nonsense codon

Summary

Summary: A codon that has been converted to the same sequence as a stop codon (CODON, TERMINATOR) by a nonsense mutation. It is different from a stop codon in that it occurs abnormally and causes premature termination of protein translation resulting in the production of truncated proteins which may be non-functional.

Top Publications

  1. ncbi PTC124 targets genetic disorders caused by nonsense mutations
    Ellen M Welch
    PTC Therapeutics, 100 Corporate Court, South Plainfield, New Jersey 07080, USA
    Nature 447:87-91. 2007
  2. ncbi Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise
    Joshua T Mendell
    Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Building, 733 N Broadway, Baltimore, Maryland 21205, USA
    Nat Genet 36:1073-8. 2004
  3. pmc Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
    Isao Kashima
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Genes Dev 20:355-67. 2006
  4. ncbi Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function
    Olaf Isken
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Genes Dev 21:1833-56. 2007
  5. ncbi Execution of nonsense-mediated mRNA decay: what defines a substrate?
    Indrani Rebbapragada
    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Curr Opin Cell Biol 21:394-402. 2009
  6. ncbi Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7
    Tetsuo Ohnishi
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Mol Cell 12:1187-200. 2003
  7. ncbi Nonsense-mediated decay approaches the clinic
    Jill A Holbrook
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D 69120 Heidelberg, Germany
    Nat Genet 36:801-8. 2004
  8. pmc Genome-wide identification of alternative splice forms down-regulated by nonsense-mediated mRNA decay in Drosophila
    Kasper Daniel Hansen
    Division of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, CA, USA
    PLoS Genet 5:e1000525. 2009
  9. ncbi SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells
    Andrea B Eberle
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Nat Struct Mol Biol 16:49-55. 2009
  10. ncbi Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast
    Feng He
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Mol Cell 12:1439-52. 2003

Detail Information

Publications268 found, 100 shown here

  1. ncbi PTC124 targets genetic disorders caused by nonsense mutations
    Ellen M Welch
    PTC Therapeutics, 100 Corporate Court, South Plainfield, New Jersey 07080, USA
    Nature 447:87-91. 2007
    ....
  2. ncbi Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise
    Joshua T Mendell
    Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Building, 733 N Broadway, Baltimore, Maryland 21205, USA
    Nat Genet 36:1073-8. 2004
    ....
  3. pmc Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
    Isao Kashima
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Genes Dev 20:355-67. 2006
    ..Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD...
  4. ncbi Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function
    Olaf Isken
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Genes Dev 21:1833-56. 2007
    ..Along with other types of quality control that occur during the complex processes of mRNA biogenesis, these mRNA surveillance mechanisms help to ensure the integrity of protein-encoding gene expression...
  5. ncbi Execution of nonsense-mediated mRNA decay: what defines a substrate?
    Indrani Rebbapragada
    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Curr Opin Cell Biol 21:394-402. 2009
    ..This leads to mRNA decay following translational repression. Recent evidence suggests that in Drosophila and human cells, decay is initiated by the endonuclease Smg6...
  6. ncbi Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7
    Tetsuo Ohnishi
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Mol Cell 12:1187-200. 2003
    ..We propose that sequential phosphorylation and dephosphorylation of hUPF1 by hSMG-1 and PP2A, respectively, contribute to the remodeling of the mRNA surveillance complex...
  7. ncbi Nonsense-mediated decay approaches the clinic
    Jill A Holbrook
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D 69120 Heidelberg, Germany
    Nat Genet 36:801-8. 2004
    ..Potential 'NMD therapeutics' will therefore need to strike a balance between the general physiological benefits of NMD and its detrimental effects in cases of specific genetic mutations...
  8. pmc Genome-wide identification of alternative splice forms down-regulated by nonsense-mediated mRNA decay in Drosophila
    Kasper Daniel Hansen
    Division of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, CA, USA
    PLoS Genet 5:e1000525. 2009
    ..Most notably, we found that the NMD-target mRNAs had significantly longer 3' untranslated regions (UTRs) than the nontarget isoforms of the same genes, supporting a role for 3' UTR length in the recognition of NMD targets in fly...
  9. ncbi SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells
    Andrea B Eberle
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Nat Struct Mol Biol 16:49-55. 2009
    ..Our data lead to a revised mechanistic model for degradation of nonsense mRNA in human cells and suggest that endonucleolytic cleavage is a conserved feature in metazoan NMD...
  10. ncbi Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast
    Feng He
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Mol Cell 12:1439-52. 2003
    ....
  11. pmc PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model
    Ming Du
    Department of Microbiology and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Proc Natl Acad Sci U S A 105:2064-9. 2008
    ....
  12. ncbi A faux 3'-UTR promotes aberrant termination and triggers nonsense-mediated mRNA decay
    Nadia Amrani
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 0122, USA
    Nature 432:112-8. 2004
    ..This anomaly depends on prior nonsense codon recognition and is eliminated in extracts derived from cells lacking the principal NMD factor, Upf1p, or by ..
  13. ncbi mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons
    Isabelle Behm-Ansmant
    MPI for Developmental Biology, Spemannstrasse 35, D 72076 Tubingen, Germany
    FEBS Lett 581:2845-53. 2007
    ..These studies are providing important insights that will aid the development of new treatments for at least some human genetic diseases...
  14. ncbi SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway
    Noemi Fukuhara
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Mol Cell 17:537-47. 2005
    ..The 14-3-3 site of SMG7 is conserved in SMG5 and SMG6. These data also imply that the homologous human Est1 might have a 14-3-3 function at telomeres, and that phosphorylation events may be important for telomerase regulation...
  15. pmc Inter-kingdom conservation of mechanism of nonsense-mediated mRNA decay
    Zoltán Kerényi
    Agricultural Biotechnology Center, Godollo, Hungary
    EMBO J 27:1585-95. 2008
    ..We propose that a complex, autoregulated NMD mechanism operated in stem eukaryotes, and that despite aspect of the mechanism being simplified in different lineages, feedback regulation was retained in all kingdoms...
  16. ncbi PAX6 mutations reviewed
    J Prosser
    MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
    Hum Mutat 11:93-108. 1998
    ..In a gene with such extraordinarily high sequence conservation throughout evolution, there are presumed undiscovered missense mutations, these are hypothesized to exist in as-yet unidentified phenotypes...
  17. ncbi Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon
    J Lykke-Andersen
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Cell 103:1121-31. 2000
    ..These data suggest that assembly of a dynamic hUpf complex initiates in the nucleus at mRNA exon-exon junctions and triggers NMD in the cytoplasm when recognized downstream of a translation termination site...
  18. ncbi Y14 and hUpf3b form an NMD-activating complex
    Niels H Gehring
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany
    Mol Cell 11:939-49. 2003
    ..These results uncover a direct role of Y14 in NMD and suggest an unexpected hierarchy in the assembly of NMD complexes...
  19. ncbi Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations
    Michael Wilschanski
    Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Jerusalem, Israel
    N Engl J Med 349:1433-41. 2003
    ..We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels...
  20. pmc Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans
    Benjamin P Lewis
    Department of Plant and Microbial Biology, Graduate Group, University of California, Berkeley, 94720, USA
    Proc Natl Acad Sci U S A 100:189-92. 2003
    ..We propose that regulated unproductive splicing and translation (RUST), through the coupling of alternative splicing and NMD, may be a pervasive, underappreciated means of regulating protein expression...
  21. ncbi Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability
    S M Medghalchi
    Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 10:99-105. 2001
    ..These data suggest that NMD is essential for mammalian cellular viability and support a critical role for the pathway in the regulated expression of selected physiologic transcripts...
  22. ncbi Aminoglycoside-induced translational read-through in disease: overcoming nonsense mutations by pharmacogenetic therapy
    L V Zingman
    Marriott Heart Disease Research Program, Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
    Clin Pharmacol Ther 81:99-103. 2007
    ..The challenge ahead is to maximize efficacy while preventing interaction with normal protein production and function...
  23. ncbi Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics
    Lynne E Maquat
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, New York 14642, USA
    Nat Rev Mol Cell Biol 5:89-99. 2004
    ..The acquisition and loss of mRNA-associated proteins accompanies the transition from the pioneer round to subsequent rounds of translation, and from translational competence to substrate for nonsense-mediated mRNA decay...
  24. ncbi UPF1 is required for nonsense-mediated mRNA decay (NMD) and RNAi in Arabidopsis
    Luis Arciga-Reyes
    Centre for Plant Sciences, University of Leeds, Leeds LS2 9JT, UK
    Plant J 47:480-9. 2006
    ..Finally, gene silencing by an inverted repeat transgene is impaired in upf1-5 mutants, indicating a connection between UPF1 and RNA interference in plants...
  25. ncbi Nonsense-mediated mRNA decay: terminating erroneous gene expression
    Kristian E Baker
    Howard Hughes Medical Institute, University of Arizona, 1007 East Lowell Street, Tucson, Arizona 85721, USA
    Curr Opin Cell Biol 16:293-9. 2004
    ..Aberrant termination then leads to both translational repression and an increased susceptibility of the mRNA to multiple ribonucleases...
  26. ncbi Communication with the exon-junction complex and activation of nonsense-mediated decay by human Upf proteins occur in the cytoplasm
    Guramrit Singh
    Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Mol Cell 27:780-92. 2007
    ..Furthermore, retention of the NMD factor hUpf1 in the nucleus strongly impairs NMD. These observations suggest that the hUpf complex communicates with the EJC and triggers NMD in the cytoplasm...
  27. pmc Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay
    Julie Z Ni
    Center for Molecular Biology of RNA and Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz, Santa Cruz, California 95064, USA
    Genes Dev 21:708-18. 2007
    ....
  28. pmc mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae
    Jeffrey N Dahlseid
    Department of Chemistry, St Olaf College, Northfield, Minnesota 55057, USA
    Eukaryot Cell 2:134-42. 2003
    ..Together, these results suggest that NMD maintains the balance of gene products that control telomere length and telomeric silencing primarily by maintaining appropriate levels of STN1, TEN1, and EST2 mRNA...
  29. ncbi Introducing sense into nonsense in treatments of human genetic diseases
    Liat Linde
    Department of Genetics, The Life Sciences Institute, Givat Ram Campus, The Hebrew University, Jerusalem 91904, Israel
    Trends Genet 24:552-63. 2008
    ..A deeper understanding of the molecular basis for variable response to readthrough of PTCs is necessary so that appropriate therapies can be developed to treat many human genetic diseases caused by PTCs...
  30. ncbi The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay
    C I Gonzalez
    Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA
    Mol Cell 5:489-99. 2000
    ..In yeast, it has been proposed that a surveillance complex searches 3' of a nonsense codon for a downstream sequence element (DSE) associated with RNA-binding proteins...
  31. pmc Both introns and long 3'-UTRs operate as cis-acting elements to trigger nonsense-mediated decay in plants
    Sándor Kertész
    Agricultural Biotechnology Center, Godollo, Hungary
    Nucleic Acids Res 34:6147-57. 2006
    ..We have also identified plant UPF1 and showed that tethering of UPF1 to either the 5'- or 3'-UTR of an mRNA results in reduced transcript accumulation. Thus, plant UPF1 might bind to mRNA in a late, irreversible phase of NMD...
  32. pmc The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex
    Shang Yi Chiu
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Genes Dev 18:745-54. 2004
    ..Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts...
  33. ncbi Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20
    Y Ishigaki
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, NY 14642, USA
    Cell 106:607-17. 2001
    ..They also indicate that CBP80-bound mRNA undergoes a "pioneer" round of translation, before CBP80-CBP20 are replaced by eIF4E, and Upf2 and Upf3 proteins dissociate from upstream of exon-exon junctions...
  34. ncbi CBP80 promotes interaction of Upf1 with Upf2 during nonsense-mediated mRNA decay in mammalian cells
    Nao Hosoda
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, New York 14642, USA
    Nat Struct Mol Biol 12:893-901. 2005
    ..SMD depends on the recruitment of Upf1 by the RNA-binding protein Stau1 but does not depend on the other Upf proteins. We find that CBP80 interacts with Upf1 and promotes the interaction of Upf1 with Upf2 but not with Stau1...
  35. pmc Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies
    Sebastien Durand
    Centre National de la Recherche Scientifique, Institut de Genetique Moleculaire de Montpellier, Universite de Montpellier, Montpellier F 34293, France
    J Cell Biol 178:1145-60. 2007
    ..The results suggest a model in which mRNA and NMD factors are sequentially recruited to P-bodies...
  36. ncbi Arabidopsis UPF1 RNA helicase for nonsense-mediated mRNA decay is involved in seed size control and is essential for growth
    Masato Yoine
    Laboratory of Biochemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464 8601 Japan
    Plant Cell Physiol 47:572-80. 2006
    ..These results suggest that the lba1 mutation in AtUPF1 maternally affects seed development and that AtUPF1 is essential for seedling growth...
  37. pmc X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment
    Leanne M Dibbens
    Department of Genetic Medicine, Level 9 Rieger Building, Women s and Children s Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia
    Nat Genet 40:776-81. 2008
    ..PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation...
  38. pmc NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements
    Joachim Weischenfeldt
    Section for Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark
    Genes Dev 22:1381-96. 2008
    ..Collectively, our data demonstrate a unique requirement of NMD for organismal survival...
  39. pmc Hypoxic inhibition of nonsense-mediated RNA decay regulates gene expression and the integrated stress response
    Lawrence B Gardner
    New York University School of Medicine, Department of Medicine, Division of Hematology, New York City, New York 10016, USA
    Mol Cell Biol 28:3729-41. 2008
    ..Our demonstration that NMD is inhibited in hypoxic cells reveals that the regulation of NMD can dynamically alter gene expression and also establishes a novel mechanism for hypoxic gene regulation...
  40. ncbi EYS is a major gene for rod-cone dystrophies in France
    Isabelle Audo
    INSERM U968, Department of Genetics, Institut de la Vision, UPMC Univ Paris 06, 17 rue Moreau, Paris, France
    Hum Mutat 31:E1406-35. 2010
    ..With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere...
  41. pmc Identification of a 2 Mb human ortholog of Drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa
    Rob W J Collin
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands
    Am J Hum Genet 83:594-603. 2008
    ..With a size of 2 Mb, it is one of the largest human genes, and it is by far the largest retinal dystrophy gene. The discovery of EYS might shed light on a critical component of photoreceptor morphogenesis...
  42. pmc Regulation of multiple core spliceosomal proteins by alternative splicing-coupled nonsense-mediated mRNA decay
    Arneet L Saltzman
    Department of Molecular Genetics, Centre for Cellular and Biomolecular Research, 160 College Street, University of Toronto, Toronto, Ontario M5S 3E1, Canada
    Mol Cell Biol 28:4320-30. 2008
    ..The results further implicate general spliceosomal components in AS regulation...
  43. ncbi Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment
    L Bidou
    1CNRS UMR 8621, Institut de Genetique et Microbiologie, Universite Paris Sud, Orsay Cedex, France
    Gene Ther 11:619-27. 2004
    ....
  44. ncbi Tissue-specific RNA surveillance? Nonsense-mediated mRNA decay causes collagen X haploinsufficiency in Schmid metaphyseal chondrodysplasia cartilage
    John F Bateman
    Cell and Matrix Biology Research Unit, Murdoch Childrens Research Institute and Department of Paediatrics, University of Melbourne, Royal Children s Hospital, Parkville, Victoria 3052, Australia
    Hum Mol Genet 12:217-25. 2003
    ....
  45. ncbi Nonsense-mediated mRNA decay (NMD) silences the accumulation of aberrant trypsin proteinase inhibitor mRNA in Nicotiana attenuata
    Jianqiang Wu
    Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, Beutenberg Campus, Hans Knoll Strasse 8, D 07745 Jena, Germany
    Plant J 51:693-706. 2007
    ..Taken together, these results highlight the complexity of the NMD activation mechanisms in plants...
  46. ncbi Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema
    Aileen Sandilands
    Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Nat Genet 39:650-4. 2007
    ..i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles...
  47. pmc Saccharomyces cerevisiae Ebs1p is a putative ortholog of human Smg7 and promotes nonsense-mediated mRNA decay
    Brian Luke
    Swiss Institute for Experimental Cancer Research ISREC, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    Nucleic Acids Res 35:7688-97. 2007
    ..Overall our findings suggest that NMD is more conserved in evolution than previously thought, and that at least one of the Smg5-7 proteins is conserved in budding yeast...
  48. pmc Long 3'-UTRs target wild-type mRNAs for nonsense-mediated mRNA decay in Saccharomyces cerevisiae
    Bessie W Kebaara
    School of Biological Sciences, University of Nebraska Lincoln, Lincoln, NE 68588, USA
    Nucleic Acids Res 37:2771-8. 2009
    ..Finally, we show that nmd mutants are sensitive to Calcofluor White, which suggests that the regulation of PGA1 and other cell wall biosynthesis proteins by NMD is physiologically significant...
  49. ncbi The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon
    Monique Buisson
    Laboratoire de Genetique Moleculaire, Signalisation et Cancer Unité Mixte de Recherche 5201 Centre National de la Recherche Scientifique, Universite Claude Bernard Lyon I, Lyon, France
    Hum Mutat 27:1024-9. 2006
    ..We show here that in the presence of a (PTC) at position 36 or 39, translation reinitiation occurs in the BRCA1 minigenes at position 128...
  50. pmc SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan
    Eric Huntzinger
    Max Planck Institute for Developmental Biology, D 72076 Tubingen, Germany
    RNA 14:2609-17. 2008
    ..degradation of PTC-containing messages is initiated by endonucleolytic cleavage in the vicinity of the nonsense codon. The endonuclease responsible for this cleavage has not been identified...
  51. pmc Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway
    Dasa Longman
    Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland, United Kingdom
    Genes Dev 21:1075-85. 2007
    ..elegans that we have termed smgl (for smg lethal). We show that the encoded proteins are conserved throughout evolution and are required for NMD in C. elegans and also in human cells...
  52. ncbi Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model
    Ming Du
    Department of Microbiology, The University of Alabama at Birmingham, 35294 2170, USA
    J Mol Med (Berl) 84:573-82. 2006
    ..Because amikacin is also less toxic than gentamicin, it may represent a superior choice for suppression therapy in patients that carry a premature stop mutation in the CFTR gene...
  53. ncbi Aberrant termination triggers nonsense-mediated mRNA decay
    N Amrani
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655 0122, USA
    Biochem Soc Trans 34:39-42. 2006
    ..Thus NMD appears to be triggered by a ribosome's failure to terminate adjacent to a properly configured 3'-UTR (untranslated region), an event that may promote binding of the UPF/NMD factors to stimulate mRNA decapping...
  54. ncbi Stop-codon read-through for patients affected by a lysosomal storage disorder
    Doug A Brooks
    Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women s Health Service, 72 King William Rd, North Adelaide, South Australia 5006, Australia
    Trends Mol Med 12:367-73. 2006
    ....
  55. ncbi Relationship between yeast polyribosomes and Upf proteins required for nonsense mRNA decay
    A L Atkin
    School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588 0666, USA
    J Biol Chem 272:22163-72. 1997
    ..Our results suggest that the association of Upf2p with polyribosomes typically found in a wild-type strain depends on the presence and opposing effects of Upf1p and Upf3p...
  56. pmc hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay
    Jürgen Wittmann
    Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger Center, University of Erlangen Nurnberg, Glückstrasse 6, D 91054 Erlangen, Germany
    Mol Cell Biol 26:1272-87. 2006
    ..Hence, NMD is important not only for maintaining the transcriptome integrity by removing nonfunctional and aberrant PTC-bearing transcripts but also for posttranscriptional control of selected physiologic transcripts with NMD features...
  57. ncbi Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities
    Fabrice Lejeune
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, NY 14642, USA
    Mol Cell 12:675-87. 2003
    ..From these and other data, we conclude that NMD in mammalian cells degrades mRNAs from both 5' and 3' ends by recruiting decapping and 5'-->3' exonuclease activities as well as deadenylating and 3'-->5' exonuclease activities...
  58. pmc Nonsense-mediated mRNA decay factors act in concert to regulate common mRNA targets
    Jan Rehwinkel
    European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
    RNA 11:1530-44. 2005
    ..Thus phenotypic differences observed across species following inhibition of NMD can be largely attributed to changes in the repertoire of regulated genes...
  59. pmc Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin
    Liat Linde
    Department of Genetics, Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel
    J Clin Invest 117:683-92. 2007
    ..Together our results suggest that the efficiency of NMD might vary and hence have an important role in governing the response to treatments aiming to promote readthrough of PTCs in many genetic diseases...
  60. pmc Nonsense-mediated mRNA decay: from vacuum cleaner to Swiss army knife
    Gabriele Neu-Yilik
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
    Genome Biol 5:218. 2004
    ..Two new approaches have identified physiological NMD substrates, and suggest that NMD functions as a multipurpose tool in the modulation of gene expression...
  61. pmc Stop codons affect 5' splice site selection by surveillance of splicing
    Binghui Li
    Department of Genetics, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 99:5277-82. 2002
    ..This notion is highly important for accurate gene expression, as perturbations that would lead to splicing at these latent sites are expected to introduce in-frame stop codons into the majority of mRNAs...
  62. ncbi Novel and de-novo truncating PAX6 mutations and ocular phenotypes in Thai aniridia patients
    La ongsri Atchaneeyasakul
    Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkok Noi, Bangkok 10700, Thailand
    Ophthalmic Genet 27:21-7. 2006
    ..To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients...
  63. pmc In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study
    Isabelle Sermet-Gaudelus
    Centre de Ressources et de Compétence en Mucoviscidose, Hopital Necker Enfants Malades, AP HP, Paris, France
    BMC Med 5:5. 2007
    ..Our pilot study was conducted to determine whether intravenous gentamicin suppresses stop codons in CF patients and whether it has clinical benefits...
  64. ncbi Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial
    Eitan Kerem
    Hadassah Hebrew University Hospital, Jerusalem, Israel
    Lancet 372:719-27. 2008
    ..PTC124 is an orally bioavailable small molecule that is designed to induce ribosomes to selectively read through premature stop codons during mRNA translation, to produce functional CFTR...
  65. ncbi The mammalian nonsense-mediated mRNA decay pathway: to decay or not to decay! Which players make the decision?
    Ana Luisa Silva
    Centro de Genética Humana, Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal
    FEBS Lett 583:499-505. 2009
    ....
  66. ncbi Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells
    Fabrice Lejeune
    Department of Biochemistry and Biophysics, University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA
    Curr Opin Cell Biol 17:309-15. 2005
    Nonsense-mediated mRNA decay (NMD) generally involves nonsense codon recognition by translating ribosomes at a position approximately 25 nts upstream of a splicing-generated exon junction complex of proteins...
  67. ncbi Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes
    Marc Buhler
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Mol Cell 18:307-17. 2005
    ..Remarkably, NMTGS is inhibited by overexpression of the putative siRNase 3'hExo, suggesting that siRNA-like molecules are involved in NMTGS...
  68. pmc Role for Upf2p phosphorylation in Saccharomyces cerevisiae nonsense-mediated mRNA decay
    Weirong Wang
    Department of Biology, University of Puerto Rico, San Juan, PR 00931
    Mol Cell Biol 26:3390-400. 2006
    ..Our results indicate that phosphorylation of UPF1 and UPF2 is a conserved event in eukaryotes and for the first time provide evidence that Upf2p phosphorylation is crucial for NMD...
  69. pmc Widespread impact of nonsense-mediated mRNA decay on the yeast intronome
    Shakir Sayani
    Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095 1569, USA
    Mol Cell 31:360-70. 2008
    ..These results show that NMD has a wider impact than previously thought on the degradation of yeast-unspliced transcripts and plays an important role in discarding precursors of regulated or suboptimally spliced transcripts...
  70. pmc Cellular mutants define a common mRNA degradation pathway targeting cytokine AU-rich elements
    G Stoecklin
    Institute of Medical Microbiology, University of Basel, Switzerland
    RNA 7:1578-88. 2001
    ..In contrast, c-fos ARE-directed mRNA degradation proceeds through a different pathway not affected by these kinases...
  71. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
    ..As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored...
  72. ncbi Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay
    Jun Wang
    Department of Immunology, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cell 10:951-7. 2002
    ..Our results suggest that NAS and NMD are distinct mechanisms despite being triggered by the same signal...
  73. ncbi Adding amino acids with novel reactivity to the genetic code of Saccharomyces cerevisiae
    Alexander Deiters
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 125:11782-3. 2003
    ..As an example, we have shown that proteins containing these amino acids can be efficiently bioconjugated with small organic molecules by a [3 + 2] cycloaddition reaction that is mild enough for the manipulation of biological samples...
  74. ncbi Genetic susceptibility to symptomatic norovirus infection in Nicaragua
    Filemon Bucardo
    Department of Microbiology, University of Leon, Nicaragua UNAN León
    J Med Virol 81:728-35. 2009
    ..151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European...
  75. ncbi Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease genes
    Richard E Green
    Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720, USA
    Bioinformatics 19:i118-21. 2003
    ..Our initial experimental studies are consistent with these predictions and suggest an unappreciated role for NMD in several human diseases...
  76. ncbi Failsafe nonsense-mediated mRNA decay does not detectably target eIF4E-bound mRNA
    Daiki Matsuda
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA
    Nat Struct Mol Biol 14:974-9. 2007
    ..CBP80-CBP20 (CBP80/20) and typically has at least one exon junction complex (EJC) situated downstream of the nonsense codon and added post-splicing...
  77. ncbi Does the nonsense-mediated mRNA decay mechanism prevent the synthesis of truncated BRCA1, CHK2, and p53 proteins?
    Olga Anczukow
    Laboratoire de Genetique Moleculaire, Signalisation et Cancer UMR5201 CNRS, Universite Lyon 1, Lyon, France
    Hum Mutat 29:65-73. 2008
    ..Therefore, our results show that it is not possible to infer the presence of truncated proteins in cells from carriers of a truncated mutation without experimental verification, as each case is expected to be different...
  78. pmc Gene set coregulated by the Saccharomyces cerevisiae nonsense-mediated mRNA decay pathway
    Rachel Taylor
    School of Biological Sciences, University of Nebraska Lincoln, NE 68588 0666, USA
    Eukaryot Cell 4:2066-77. 2005
    ..This strategy is significant because it allows us to classify the genes regulated by NMD into functionally related sets, an important step toward understanding the role NMD plays in the normal functioning of yeast cells...
  79. pmc High resolution transcriptome maps for wild-type and nonsense-mediated decay-defective Caenorhabditis elegans
    Arun K Ramani
    Donnelly CCBR, College Street, University of Toronto, Toronto, M5S 3E1, Canada
    Genome Biol 10:R101. 2009
    ..We utilized this framework to identify transcriptome changes in animals lacking the nonsense-mediated decay (NMD) pathway...
  80. ncbi Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species
    Elena Conti
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Curr Opin Cell Biol 17:316-25. 2005
    ..With the elucidation of the first crystal structures of components of the NMD machinery, the way is paved towards a molecular understanding of the protein interaction network underlying this process...
  81. pmc Global analysis of alternative splicing uncovers developmental regulation of nonsense-mediated decay in C. elegans
    Sergio Barberan-Soler
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA
    RNA 15:1652-60. 2009
    ..We propose that NMD of certain alternatively spliced isoforms is regulated, and that some stabilized NMD targets may be translated...
  82. ncbi Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease
    Mehrdad Khajavi
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Eur J Hum Genet 14:1074-81. 2006
    ..Here, we review the physiological role of this surveillance pathway, its implications for human diseases, and why knowledge of NMD is important to an understanding of genotype-phenotype correlations in various genetic disorders...
  83. ncbi Nonsense-mediated mRNA decay in mammals
    Lynne E Maquat
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, 601 Elmwood Avenue, Box 712, University of Rochester, Rochester, NY 14642, USA
    J Cell Sci 118:1773-6. 2005
  84. ncbi Eukaryotic mRNA decapping
    Jeff Coller
    Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA
    Annu Rev Biochem 73:861-90. 2004
    ..We discuss the decapping process in the light of these central properties, which also suggest fundamental aspects of cytoplasmic mRNA physiology that connect decapping, translation, and storage of mRNA...
  85. ncbi The role of SMG-1 in nonsense-mediated mRNA decay
    Akio Yamashita
    Department of Molecular Biology, Yokohama City University School of Medicine and Graduate School of Medical Science, Kanazawa Ku, Yokohama 236 0004, Japan
    Biochim Biophys Acta 1754:305-15. 2005
    ..At present, a variety of tools are available that can specifically suppress NMD, and it is possible to examine the contribution of NMD in a variety of physiological and pathological conditions...
  86. pmc Ebs1p, a negative regulator of gene expression controlled by the Upf proteins in the yeast Saccharomyces cerevisiae
    Amanda S Ford
    Laboratories of Genetics and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA
    Eukaryot Cell 5:301-12. 2006
    ..Finally, EBS1 transcript levels are under the control of nonsense-mediated mRNA decay (NMD), providing the first example of an NMD-sensitive transcript whose protein product influences a step in gene expression required for NMD...
  87. ncbi Alternatively spliced TCR mRNA induced by disruption of reading frame
    Jun Wang
    Department of Immunology, The University of Texas M D Anderson Cancer Center, Box 180, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Science 297:108-10. 2002
    ..The finding that translation signals regulate the levels of alternatively spliced mRNAs generated in the nucleus may alter the current view of how gene expression is controlled in eukaryotic cells...
  88. ncbi The lba1 mutation of UPF1 RNA helicase involved in nonsense-mediated mRNA decay causes pleiotropic phenotypic changes and altered sugar signalling in Arabidopsis
    Masato Yoine
    Laboratory of Biochemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464 8601, Japan
    Plant J 47:49-62. 2006
    ..The lba1 mutant provides a good tool for studying NMD in plants...
  89. pmc Caenorhabditis elegans SMG-2 selectively marks mRNAs containing premature translation termination codons
    Lisa Johns
    Department of Genetics, University of Wisconsin, Madison, WI 53706, USA
    Mol Cell Biol 27:5630-8. 2007
    ..We discuss these observations with regard to the functions of SMG-2 and its phosphorylation during NMD...
  90. pmc Posttranscriptional gene regulation by spatial rearrangement of the 3' untranslated region
    Andrea B Eberle
    Institute of Cell Biology, University of Berne, Berne, Switzerland
    PLoS Biol 6:e92. 2008
    ..Most importantly, our results demonstrate that spatial rearrangements of the 3' untranslated region can modulate the NMD pathway and thereby provide a novel mechanism for posttranscriptional gene regulation...
  91. pmc TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy
    Sylvain Hanein
    Département de génétique, Universite Paris Descartes, Unité INSERM U781, Hopital Necker Enfants Malades, 75015 Paris, France
    Am J Hum Genet 84:493-8. 2009
    ....
  92. pmc An alternative branch of the nonsense-mediated decay pathway
    Wai Kin Chan
    Department of Biochemistry and Molecular Biology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    EMBO J 26:1820-30. 2007
    ....
  93. ncbi The human intronless melanocortin 4-receptor gene is NMD insensitive
    Katja S Brocke
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Hum Mol Genet 11:331-5. 2002
    ..Thus, the naturally intronless MC4-R gene and probably many other intronless genes fail to be monitored by the NMD pathway...
  94. pmc Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation
    Joachim B Kunz
    Department for Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany
    RNA 12:1015-22. 2006
    ..Stimulation of translation is independent of this interaction and is determined by other regions of the hUpf3 protein, indicating the presence of different downstream pathways of hUpf3 proteins either in NMD or in translation...
  95. ncbi Nonsense-mediated translational repression involves exon junction complex downstream of premature translation termination codon
    Hyung Chul Lee
    School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
    FEBS Lett 584:795-800. 2010
    ..Our findings implicate EJCs or core EJC components as negative regulators of translation...
  96. pmc A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family
    Ke Yao
    Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China
    Mol Vis 14:1272-6. 2008
    ..To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family...
  97. pmc The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway
    Marcelo H Viegas
    Department of Pediatric Oncology, Hematology and Immunology, Children s Hospital, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
    Nucleic Acids Res 35:4542-51. 2007
    ..We conclude that cellular concentrations of RNPS1 can modify NMD efficiency and propose that cell type specific co-factor availability represents a novel principle that controls NMD...
  98. pmc An unappreciated role for RNA surveillance
    R Tyler Hillman
    Department of Bioengineering, University of California, Berkeley, CA 94720 3102, USA
    Genome Biol 5:R8. 2004
    ....
  99. pmc Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay
    Ana Luisa Silva
    Centro de Genética Humana, Instituto Nacional de Saude Dr Ricardo Jorge, 1649 016 Lisboa, Portugal
    RNA 14:563-76. 2008
    ..These results reveal a novel parameter of NMD in mammalian cells that can account for the stability of mRNAs with AUG-proximal PTCs. These findings serve to expand current mechanistic models of NMD and mRNA translation...
  100. ncbi ASPM is a major determinant of cerebral cortical size
    Jacquelyn Bond
    Molecular Medicine Unit, University of Leeds, St James s University Hospital, Beckett Street, Leeds LS9 7TF, UK
    Nat Genet 32:316-20. 2002
    ..Our results and evolutionary considerations suggest that brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells...
  101. ncbi mRNA surveillance of expressed pseudogenes in C. elegans
    Quinn M Mitrovich
    Department of Genetics, University of Wisconsin, Madison 53706, USA
    Curr Biol 15:963-7. 2005
    ..We describe an expressed pseudogene that encodes a small nucleolar RNA (snoRNA) within an intron and suggest this represents an evolutionary intermediate between snoRNA-encoding host genes that do or do not encode proteins...

Research Grants62

  1. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..The proposed studies are aimed at understanding basic cellular mechanisms of gene expression, and may provide the basis for developing or improving diagnostic tools and therapeutic agents for these diseases. ..
  2. Novel Collagen II Alternative Transcripts and Mouse Skeletal Development
    Audrey McAlinden; Fiscal Year: 2010
    ..Additional work on this project will investigate the mechanisms for regulating the amount of each alternatively spliced mRNA type during differentiation and development. ..
  3. Role of Intronic Variants Affecting Splicing in Juvenile Myoclonic Epilepsy
    Debra J Wolgemuth; Fiscal Year: 2010
    ....
  4. Aminoglycoside microbicides restore natural expression of anti-HIV-1 retrocyclins
    Alexander M Cole; Fiscal Year: 2010
    ..Aminoglycoside-mediated translation of retrocyclins could result in a new class of microbicide to prevent HIV-1 transmission. ..
  5. Aminoglycoside microbicides restore natural expression of anti-HIV-1 retrocyclins
    ALEXANDER MICHAEL COLE; Fiscal Year: 2013
    ..Aminoglycoside-mediated translation of retrocyclins could result in a new class of microbicide to prevent HIV-1 transmission. ..
  6. Presenilin 2 and Neuroinflammation
    Suman Jayadev; Fiscal Year: 2013
    ....
  7. Expressing New Tumor Antigens by Inhibition of Nonsense Mediated mRNA Decay
    Eli Gilboa; Fiscal Year: 2013
    ....
  8. Identification of Genes Involved in FHLH
    Janos Sumegi; Fiscal Year: 2010
    ..3-22 and 11q25 and among genes coding for SNARE proteins essential for direct, controlled and very rapid fusion of phospholipids membranes. ..
  9. Retrocyclins: Circular Defensins Active Against HIV-1
    ALEXANDER MICHAEL COLE; Fiscal Year: 2011
    ..abstract_text> ..
  10. Retrocyclins: Circular Defensins Active Against HIV-1
    Alexander M Cole; Fiscal Year: 2010
    ..Availability of such agents, in the form of a cream or gel, would empower vulnerable sexual partners by providing them with an invisible, effective means of protection. ..
  11. Nonsense codon activation of endonuclease-mediated mRNA decay
    Daniel R Schoenberg; Fiscal Year: 2012
    ..The long-term goal of this research is to develop new treatments for beta-thalassemia by understanding the novel mechanisms involved in beta-globin mRNA decay in erythroid cells. ..
  12. Recognition and degradation of mRNA by nonsense-mediated decay
    KRISTIAN EILEEN BAKER; Fiscal Year: 2013
    ..cells a specialized pathway has evolved to stimulate the degradation of aberrant mRNAs containing a premature nonsense codon (PTC), a signal that causes early termination of translation and, if left unchecked, the accumulation of ..
  13. Retroviral Regulatory Sequences with Coding Sequences
    Karen L Beemon; Fiscal Year: 2013
    ..Initial studies will be carried out with RSV but extended to a number of other retroviruses, including HIV-1. Intracellular sites of viral RNA decay will also be investigated. ..
  14. Preclinical Development of Uricase-PEG 20
    JOHN BOMALASKI; Fiscal Year: 2002
    ..However, in humans, the urate oxidase gene has evolved to contain a nonsense codon which results in a complete loss of enzyme activity...
  15. Clinical and Mechanistic Features of Premature Termination Codon Suppression
    STEVEN MARK ROWE; Fiscal Year: 2010
    ..Successful completion of this project will define the potential role of nonsense codon suppression as a future CF therapy...
  16. NONSENSE RNA SURVEILLANCE IN HEALTH AND DISEASE
    Harry Dietz; Fiscal Year: 2000
    ..can down regulation of NMRD by a RENT1 dominant negative rescue a disease phenotype caused by a premature nonsense codon, or even be used to detect new disease genes? The D836X nonsense mutation (or similar mutations) in the CFTR (..
  17. CONTROL OF ARG-2 GENE EXPRESSION IN NEUROSPORA
    MATTHEW SACHS; Fiscal Year: 2009
    ..stalling at the uORF termination codon in response to Arg destabilizes CPA1 mRNA by increasing the extent of nonsense codon recognition by NMD...
  18. ISOLATION & CHARACTERIZATION OF HRG4, A NEW RETINAL GENE
    George Inana; Fiscal Year: 2003
    ..To date, it has been demonstrated that: (1) a patient with late-onset cone-rod dystrophy has a nonsense codon mutation in HRG4, a photoreceptor gene identified in the investigator's laboratory; (2) a transgenic mouse ..
  19. Beta-globin mRNA decay in erythroid cells
    Daniel Schoenberg; Fiscal Year: 2005
    ..The long-term goal is to identify new therapeutic targets for treating beta-thalassemia and other diseases caused by PTCs by better understanding the enzymatic mechanisms responsible for the degradation of PTC-containing mRNAs. ..
  20. Contribution of DNA photoproducts to UV mutagenesis
    Douglas Fix; Fiscal Year: 2003
    ..This allele is defective because of a UAA nonsense codon in the mRNA encoding position 161 of the TyrA polypeptide, rendering FX-11 Tyr-...
  21. MESSENGER RNA METABOLISM IN YEAST
    Allan Jacobson; Fiscal Year: 2004
    ..decay, including poly(A) shortening, endonucleolytic cleavage, and the arrest of translation at a premature nonsense codon. Using the yeast Saccharomyces cerevisiae as a model system, work in my laboratory has shown that the latter ..
  22. PROTEIN SYNTHESIS IN ERYTHROID PRECURSORS
    Ronald Rieder; Fiscal Year: 1993
    ..A dinucleotide deletion causes a frame-shift which generates a nonsense codon in mRNA...
  23. REGULATION OF AVIAN SARCOMA VIRUS--RNA PROCESSING
    CONRAD STOLTZFUS; Fiscal Year: 1999
    ..Additional nonsense codon mutations will be constructed within the src gene coding region to determine how these mutations act to ..
  24. The Effect of Nonsense Mediated Decay on mRNA Splicing
    JENNIFER LYTLE; Fiscal Year: 2005
    ..Quantitative RT-PCR will be used to measure the abundance of introns in wildtype, nonsense codon-containing, and missense-codon containing precursor mRNAs since it has been proven mathematically that the ..
  25. SITE DIRECTED PROTEIN ANALYSIS--FUNCTIONAL IMPLICATIONS
    PRAVEEN MARAPAKA; Fiscal Year: 2000
    ..prepared by in vitro translation, where introduction of an unnatural amino acid involves suppression of a nonsense codon with a misacylated suppression tRNA...
  26. REGULATION OF NORMAL AND DEFECTIVE HUMAN GENES
    LYNNE MAQUAT; Fiscal Year: 2005
    ..elegans. Characterize the human homologue of Ubf1 and its role in NMD, in particular studying the role of its ATPase and putative helicase activities, and what cellular proteins it interacts with. ..
  27. POST-TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION
    LYNNE MAQUAT; Fiscal Year: 2002
    ....
  28. Conditional Knockout of WT1 in Sertoli Cells In Vivo
    Michelle Barton; Fiscal Year: 2007
    ..g., those expressing Cre from the Pem Pp) will be a valuable resource for selectively knocking out other genes in postnatal Sertoli cells. [unreadable] [unreadable]..
  29. Nonsense-mediated mRNA decay induced by alternative splicing
    Steven Brenner; Fiscal Year: 2008
    ..These studies will also be used to offer insight into the varied mechanisms of PTC-recognition in different species. ..
  30. Regulation of Presenilin Genes
    Evgeny Rogaev; Fiscal Year: 2008
    ..These studies will contribute to identification of molecular factors regulating the primary causes of AD, and ultimately, to the development of new strategies for prevention and rational therapy of Alzheimer's disease. ..
  31. HDAd-mediated gene therapy for hemophilia B
    Nicola Brunetti Pierri; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  32. The Challenges of Autosomal Recessive and Other New Forms of OI
    Peter Byers; Fiscal Year: 2008
    ..It also will facilitate identification of new OI genes, identify new paths of research to benefit patients, and increase progress of the Linked Clinical Research Centers. [unreadable] [unreadable] [unreadable] [unreadable]..
  33. Anaplerotic therapy in Propionic Acidemia
    Nicola Longo; Fiscal Year: 2008
    ..This approach, if effective, could be extended to a number of other diseases, including other organic acidemias and mitochondrial disorders. [unreadable] [unreadable] [unreadable]..
  34. Pathobiology of Retinal Vasculopathy with Cerebal Leukodystrophy (RVCL)
    Joanna C Jen; Fiscal Year: 2010
    ..abstract_text> ..
  35. Evolution of vertebrate sensory genes
    Jianzhi Zhang; Fiscal Year: 2010
    ..These studies will also help understand human smell and taste variations and disorders. ..
  36. Genes, Hormomes, Growth, and Body Fat: Project HeartBeat
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ..Our analyses may also help identify genetic variants that may predispose some individuals toward obesity. ..
  37. THERAPUTIC TRIAL IN PATIENTS WITH LQTS 3 GENE MUTATION
    Arthur Moss; Fiscal Year: 2002
    ..The significance of this work relates to the future use of molecular therapeutics to treat ion-channel disorders associated with congenital and acquired cardiac repolarization disorders. ..
  38. Genetic Epidemiology of Aging Skeletal Muscle
    Stephen Roth; Fiscal Year: 2007
    ..abstract_text> ..
  39. A Canine Model for Human X-Linked Ectodermal Dysplasia
    Margret Casal; Fiscal Year: 2007
    ..Furthermore, the HED dogs will be examined to demonstrate that a specific immune deficiency is responsible for pulmonary disease rather than the previously thought lack of respiratory mucoid glands. ..
  40. NONSENSE MEDIATED MRNA DECAY PATHWAY
    STUART PELTZ; Fiscal Year: 2005
    ..The goals of the experiments in this grant proposal are to investigate the sequences and factors involved in the NMD pathway in order to dissect its mechanism and how it is regulated. ..
  41. MOLECULAR GENETICS OF NAIL PATELLA SYNDROME
    Iain McIntosh; Fiscal Year: 2004
    ..Furthermore, by identification of elements controlling LMX1B expression and the factors interacting with LMX1B, a better model of limb development will be derived. ..
  42. Regulation of CFTR by adenosine, A2 receptors, and PLA2
    John Clancy; Fiscal Year: 2004
    ..The experiments outlined also identify a new way to regulate CFTR, and therefore may help define new therapeutic targets in the disease. ..
  43. Inositol defects and neuronal death in the weeble mouse
    Arne Nystuen; Fiscal Year: 2004
    ..Together these aims will provide an understanding of precisely where, when and why neurons are lost due to the loss of Inpp4a function. ..
  44. L. MONOCYTOGENES CLONAL GROUPS: ECOLOGY AND TRANSMISSION
    Martin Wiedmann; Fiscal Year: 2004
    ..4. Determine the phenotypes of L. monocytogenes clonal groups associated with specific environments and hosts and determine the genetic basis for phenotypes associated with a preference for specific habitats...
  45. Genetic Aspects of Vestibular Dysfunction
    Stephen Roth; Fiscal Year: 2004
    ..The proposed project will generate important pilot data related to the genetics of vestibular dysfunction, thus fitting within the R21 grant mechanism. ..
  46. POSITIONAL CLONING OF A GENE FOR ESSENTIAL TREMOR
    Joseph Higgins; Fiscal Year: 2004
    ..abstract_text> ..
  47. Positional cloning of a gene for mental retardation
    Joseph Higgins; Fiscal Year: 2004
    ..abstract_text> ..
  48. MRNA TURNOVER BY ELEMENTS IN PROTEIN CODING REGION
    Ann Bin Shyu; Fiscal Year: 2003
    ..They may function as cancer suppressors whose mutation can lead to deregulated protooncogene expression and subsequent cell transformation. ..
  49. Conference on Molecular Biology of the Heart
    Leslie Leinwand; Fiscal Year: 2002
    ..It will be a multidisciplinary meeting that should bring together people who are beginning to have regular dialogues but whose traditions have been somewhat separate. ..
  50. Molecular Analysis of a Canine CNS Developmental Defect
    Paula Henthorn; Fiscal Year: 2005
    ....
  51. Human and Murine Models of BRCA1 Tumorigenesis
    BERT O MALLEY; Fiscal Year: 2007
    ..abstract_text> ..
  52. Cancer Immunotherapy Targeting Endothelial Antigens
    Eli Gilboa; Fiscal Year: 2007
    ..The existence of the required expertise, infrastructure and the clinical immunotherapy programs at Duke will facilitate and expedite the clinical translation of these proof-of concept murine studies. [unreadable] [unreadable]..
  53. MODIFYING GENE DETERMINANTS OF TOOTH AND BONE PHENOTYPES
    John Wright; Fiscal Year: 2007
    ..abstract_text> ..
  54. Inflammatory Genomics in Human Carotid Artery Disease
    GAIL JARVIK; Fiscal Year: 2006
    ..Genes that are implicated in disease may eventually allow targeted therapy. ..
  55. New Research Strategies in Osteogenesis Imperfecta
    Peter Byers; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  56. Diseases of the Vestibular System
    Robert Baloh; Fiscal Year: 2006
    ..abstract_text> ..
  57. ETIOLOGY AND DEVELOPMENT OF CONGENITAL HEART DISEASE
    Paula Henthorn; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  58. International Conference on Episodic Ataxia Syndromes
    Joanna Jen; Fiscal Year: 2005
    ..abstract_text> ..
  59. Nucleic Acids with Novel Structures and Functions
    Peter Schultz; Fiscal Year: 2005
    ..In addition to the applications described above, these experiments will likely provide new insights into nucleic acid structure, function and recognition. ..
  60. COMMON POLYMORPHISM EFFECTS ON UREA CYCLE FUNCTION
    Marshall Summar; Fiscal Year: 2001
    ..Positive results in this study will lead to further study of other conditions involving the derangement of waste nitrogen disposal. ..