translational peptide chain initiation

Summary

Summary: A process of GENETIC TRANSLATION whereby the formation of a peptide chain is started. It includes assembly of the RIBOSOME components, the MESSENGER RNA coding for the polypeptide to be made, INITIATOR TRNA, and PEPTIDE INITIATION FACTORS; and placement of the first amino acid in the peptide chain. The details and components of this process are unique for prokaryotic protein biosynthesis and eukaryotic protein biosynthesis.

Top Publications

  1. ncbi eIF3: a versatile scaffold for translation initiation complexes
    Alan G Hinnebusch
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Biochem Sci 31:553-62. 2006
  2. pmc Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs
    Isabella Moll
    Max F Perutz Laboratories, Department of Microbiology and Genetics, University Department at the Vienna Biocenter, Dr Bohrgasse 9 4, 1030 Vienna, Austria
    Nucleic Acids Res 32:3354-63. 2004
  3. pmc Initiation of protein synthesis in bacteria
    Brian Søgaard Laursen
    Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10C, DK 8000 Aarhus C, Denmark
    Microbiol Mol Biol Rev 69:101-23. 2005
  4. ncbi Unfolding of mRNA secondary structure by the bacterial translation initiation complex
    Sean M Studer
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Mol Cell 22:105-15. 2006
  5. pmc Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo
    S López de Quinto
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Madrid, Spain
    RNA 6:1380-92. 2000
  6. pmc Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold
    M R Conte
    Department of Biochemistry, Imperial College of Science, Technology and Medicine, Exhibition Road, London, UK
    EMBO J 19:3132-41. 2000
  7. pmc A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo
    K Asano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA
    Genes Dev 14:2534-46. 2000
  8. pmc 5'-untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation
    Xue Qing Wang
    Department of Biochemistry and Molecular Biology, The Institute for Molecular Bioscience and The Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Queensland 4072, Australia
    Nucleic Acids Res 32:1382-91. 2004
  9. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
  10. pmc Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F
    M Piron
    Laboratoire de Virologie et Immunologie Moleculaires INRA, CRJJ, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France
    EMBO J 17:5811-21. 1998

Detail Information

Publications212 found, 100 shown here

  1. ncbi eIF3: a versatile scaffold for translation initiation complexes
    Alan G Hinnebusch
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Biochem Sci 31:553-62. 2006
    ..This location of eIF3 seems ideally suited for its other proposed regulatory functions, including reinitiating translation on polycistronic mRNAs and acting as a receptor for protein kinases that control protein synthesis...
  2. pmc Translation initiation with 70S ribosomes: an alternative pathway for leaderless mRNAs
    Isabella Moll
    Max F Perutz Laboratories, Department of Microbiology and Genetics, University Department at the Vienna Biocenter, Dr Bohrgasse 9 4, 1030 Vienna, Austria
    Nucleic Acids Res 32:3354-63. 2004
    ....
  3. pmc Initiation of protein synthesis in bacteria
    Brian Søgaard Laursen
    Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10C, DK 8000 Aarhus C, Denmark
    Microbiol Mol Biol Rev 69:101-23. 2005
    ..The future challenge is to obtain atomic-resolution structures of complete initiation complexes in order to understand the mechanism of translation initiation in molecular detail...
  4. ncbi Unfolding of mRNA secondary structure by the bacterial translation initiation complex
    Sean M Studer
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Mol Cell 22:105-15. 2006
    ..We show that unfolding of structured mRNAs requires a SD sequence, the start codon, fMet-tRNA(fMet), and the GTP bound form of initiation factor 2 bound to the 30S subunit...
  5. pmc Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo
    S López de Quinto
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Madrid, Spain
    RNA 6:1380-92. 2000
    ..The strong correlation found between eIF4G-RNA interaction and IRES activity in transfected cells suggests that eIF4G acts as a linker to recruit the translational machinery in IRES-dependent initiation...
  6. pmc Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold
    M R Conte
    Department of Biochemistry, Imperial College of Science, Technology and Medicine, Exhibition Road, London, UK
    EMBO J 19:3132-41. 2000
    ..Mutational analyses show that both RRM-3 and RRM-4 contribute to RNA binding specificity and that, despite its unusual sequence, PTB binds RNA in a manner akin to that of other RRM proteins...
  7. pmc A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo
    K Asano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA
    Genes Dev 14:2534-46. 2000
    ..We propose that the multifactor complex is an important intermediate in translation initiation in vivo...
  8. pmc 5'-untranslated regions with multiple upstream AUG codons can support low-level translation via leaky scanning and reinitiation
    Xue Qing Wang
    Department of Biochemistry and Molecular Biology, The Institute for Molecular Bioscience and The Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Queensland 4072, Australia
    Nucleic Acids Res 32:1382-91. 2004
    ..This study shows that for mRNAs containing multiple uORFs/uAUGs, ribosome reinitiation and leaky scanning are efficient mechanisms for initiation at their main AUGs...
  9. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
    ..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
  10. pmc Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F
    M Piron
    Laboratoire de Virologie et Immunologie Moleculaires INRA, CRJJ, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France
    EMBO J 17:5811-21. 1998
    ..These results also suggest that NSP3A, by taking the place of PABP on eIF4GI, is responsible for the shut-off of cellular protein synthesis...
  11. pmc Selective stimulation of translation of leaderless mRNA by initiation factor 2: evolutionary implications for translation
    S Grill
    Institute of Microbiology and Genetics, Vienna Biocenter, University of Vienna, Dr Bohrgasse 9, 1030 Vienna, Austria
    EMBO J 19:4101-10. 2000
    ....
  12. pmc A second look at cellular mRNA sequences said to function as internal ribosome entry sites
    Marilyn Kozak
    Department of Biochemistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
    Nucleic Acids Res 33:6593-602. 2005
    ..The practice of calling even very weak results 'positive' is one of the problems discussed herein. The extremely low efficiency of putative IRESs is inconsistent with their postulated biological roles.'..
  13. pmc In vitro analysis of the interaction between the small RNA SR1 and its primary target ahrC mRNA
    Nadja Heidrich
    AG Bakteriengenetik, Friedrich Schiller Universitat Jena, Philosophenweg 12, Jena D 07743, Germany
    Nucleic Acids Res 35:4331-46. 2007
    ..The intracellular concentrations of SR1 were calculated under different growth conditions...
  14. 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...
  15. pmc IRES interaction with translation initiation factors: functional characterization of novel RNA contacts with eIF3, eIF4B, and eIF4GII
    S López de Quinto
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Cantoblanco, Madrid, Spain
    RNA 7:1213-26. 2001
    ....
  16. pmc Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation
    María Inés Barría
    Laboratorio de Virologia Molecular, Centro de Investigaciones Medicas, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Nucleic Acids Res 37:957-71. 2009
    ..These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation...
  17. ncbi Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells
    Lili Zhang
    Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California 95616, USA
    J Biol Chem 282:5790-800. 2007
    ..Cancer cells appear to require an aberrantly activated translational state to survive, suggesting that the initiation factors may be promising therapeutic targets for treating cancer...
  18. ncbi Pushing the limits of the scanning mechanism for initiation of translation
    Marilyn Kozak
    Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA
    Gene 299:1-34. 2002
    ..The accumulated evidence reveals how the scanning mechanism dictates the pattern of transcription--forcing production of monocistronic mRNAs--and the pattern of translation of eukaryotic cellular and viral genes...
  19. pmc Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNA
    Dmitri E Andreev
    Belozersky Institute of Physico Chemical Biology, Moscow State University, Moscow, Russia
    RNA 13:1366-74. 2007
    ..The kinetic toeprint assay also shows that cap-dependent assembly of the 48S complex in vitro occurs faster than the FMDV IRES-mediated complex assembly...
  20. ncbi Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo
    M Kozak
    Nature 308:241-6. 1984
    ..Maximum synthesis of preproinsulin occurred when a purine, preferably adenosine, was located three nucleotides upstream from the initiator codon. Adenosine is found most frequently in that position in natural mRNAs...
  21. pmc On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation
    Byung Hoon Kim
    Department of Biochemistry, Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN 37996 0840, USA
    Genome Biol 8:R60. 2007
    ..How individual subunits of eIF3 contribute to the translation of specific mRNAs remains poorly understood, however. This is true in particular for those subunits that are not conserved in budding yeast, such as eIF3h...
  22. pmc The roles of initiation factor 2 and guanosine triphosphate in initiation of protein synthesis
    Ayman Antoun
    Department of Cell and Molecular Biology, BMC, Uppsala University, Box 596, S 75 124 Uppsala, Sweden
    EMBO J 22:5593-601. 2003
    ..Our data, indicating that eIF5B and IF2 have similar functions, are used to rationalize the phenotypes of GTPase-deficient mutants of eIF5B and IF2...
  23. pmc Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA modulates translation at the core and polymerase initiation codons
    Augustine Chen
    Biochemistry Department, University of Otago Dunedin, New Zealand
    Nucleic Acids Res 33:1169-81. 2005
    ..Our results indicate that the C0 ORF is a determinant in balancing the synthesis of the core and polymerase proteins...
  24. pmc Interaction of mitochondrial initiation factor 2 with mitochondrial fMet-tRNA
    Angela C Spencer
    Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 3290, USA
    Nucleic Acids Res 32:5464-70. 2004
    ..Finally, the region of IF-2(mt) responsible for the interaction with fMet-tRNA was mapped to the C2 sub-domain of domain VI of this factor...
  25. ncbi A sequence required for -1 ribosomal frameshifting located four kilobases downstream of the frameshift site
    C P Paul
    Plant Pathology Department, Iowa State University, Ames 50011, USA
    J Mol Biol 310:987-99. 2001
    ..Most importantly, the remarkably long-distance interaction reported here suggests the presence of a novel structure that can facilitate ribosomal frameshifting...
  26. ncbi Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site-mediated translation via phosphatidylinositol 3-kinase pathway in human factor-dependen
    Norihiko Kobayashi
    Department of Hematology, Research Institute, International Medical Center of Japan, 1 21 1 Toyama, Shinjuku ku, Tokyo 162 8655, Japan
    Blood 102:3186-95. 2003
    ..Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells...
  27. pmc Evidence for in vivo ribosome recycling, the fourth step in protein biosynthesis
    L Janosi
    Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA
    EMBO J 17:1141-51. 1998
    ..RRF inactivation was bacteriostatic in the growing phase and bactericidal during the transition between the stationary and growing phase, confirming the essential nature of the fourth step of protein synthesis in vivo...
  28. pmc Site-directed mutagenesis of a Saccharomyces cerevisiae mitochondrial translation initiation codon
    L S Folley
    Section of Genetics and Development, Cornell University, Ithaca, New York 14853 2703
    Genetics 129:659-68. 1991
    ..We conclude that, while AUG is an important component of the COX3 translation initiation site, the site probably is also specified by other sequence or structural features...
  29. pmc The hepatitis C virus 3'-untranslated region or a poly(A) tract promote efficient translation subsequent to the initiation phase
    Shelton S Bradrick
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Nucleic Acids Res 34:1293-303. 2006
    ..Analysis of post-initiation events revealed that the 3' poly(A) tract and HCV 3'-UTR improve translation efficiency by enabling termination and possibly ribosome recycling for successive rounds of translation...
  30. ncbi Re-programming of translation following cell stress allows IRES-mediated translation to predominate
    Keith A Spriggs
    School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK
    Biol Cell 100:27-38. 2008
    ..Importantly, the genes identified in each of these studies do not show a significant amount of overlap, suggesting that 10-15% of all mRNAs have the capability for their initiation to occur via alternative mechanism(s)...
  31. ncbi A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas
    S R Hann
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104
    Cell 52:185-95. 1988
    ..In Burkitt's lymphomas, the removal or specific mutation of exon 1 in c-myc translocations correlates with suppression of synthesis of the larger protein, and thus may contribute to the oncogenic activation of c-myc...
  32. ncbi Translational efficiency of a non-AUG initiation codon is significantly affected by its sequence context in yeast
    Shun Jia Chen
    Department of Life Science, National Central University, Jung li, Taiwan 32001
    J Biol Chem 283:3173-80. 2008
    ..these results suggest that sequence context is more important for translation initiation in yeast than previously appreciated...
  33. pmc Diversity of preferred nucleotide sequences around the translation initiation codon in eukaryote genomes
    So Nakagawa
    Department of Systems Biology, School of Biomedical Science, Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Tokyo, Japan
    Nucleic Acids Res 36:861-71. 2008
    ....
  34. pmc Structure and function of HCV IRES domains
    Peter J Lukavsky
    Laboratory of Molecular Biology, MRC, Hills Road, Cambridge CB2 0QH, UK
    Virus Res 139:166-71. 2009
    ....
  35. pmc Assessing IRES activity in the HIF-1alpha and other cellular 5' UTRs
    Andrew G Bert
    Division of Human Immunology, Hanson Institute, Institute of Medical and Veterinary Science IMVS, Adelaide, SA, Australia
    RNA 12:1074-83. 2006
    ..The translation of transfected monocistronic RNAs containing these cellular UTRs was greatly enhanced by the presence of a 5' cap, raising questions as to the strength or mechanism of IRES-mediated translation in these assays...
  36. pmc Divergent tRNA-like element supports initiation, elongation, and termination of protein biosynthesis
    Eric Jan
    Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 100:15410-5. 2003
    ..Thus, this P-site-occupying IRES directs the assembly of 80S ribosomes, sets the translational reading frame, and mimics the functions of both Met-tRNAi and peptidyl tRNA to support elongation and termination...
  37. ncbi STAB-SD: a Shine-Dalgarno sequence in the 5' untranslated region is a determinant of mRNA stability
    H Agaisse
    Unité de Biochimie Microbienne, Centre National de la Recherche Scientifique URA 1300, Institut Pasteur, Paris, France
    Mol Microbiol 20:633-43. 1996
    ..thuringiensis and may therefore be a widespread determinant of mRNA stability...
  38. pmc Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5' untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated
    Sergey E Dmitriev
    A N Belozersky Institute of Physico Chemical Biology, Moscow State University, Bldg A, Moscow 119992, Russia
    Mol Cell Biol 27:4685-97. 2007
    ..Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event...
  39. ncbi Divergent picornavirus IRES elements
    Graham J Belsham
    National Veterinary Institute, Technical University of Denmark, Lindholm, DK 4771 Kalvehave, Denmark
    Virus Res 139:183-92. 2009
    ..The selection of the initiation codon by these distinct IRES elements is also discussed...
  40. pmc Polypyrimidine tract-binding protein enhances the internal ribosomal entry site-dependent translation of p27Kip1 mRNA and modulates transition from G1 to S phase
    Sungchan Cho
    PBC, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790 784, South Korea
    Mol Cell Biol 25:1283-97. 2005
    ..Together, these data suggest that PTB modulates cell cycle and differentiation, at least in part, by enhancing the IRES activity of p27(Kip1) mRNA...
  41. ncbi Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection
    S López de Quinto
    Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Madrid, Cantoblanco, 28049, Spain
    Virology 255:324-36. 1999
    ..Thus our results indicate that the region located in the aphthovirus RNA between functional AUGs is involved in start codon recognition, strongly favoring selection of the second start AUG as the main initiator codon...
  42. ncbi Ribosomal initiation complexes probed by toeprinting and effect of trans-acting translational regulators in bacteria
    Pierre Fechter
    Universite de Strasbourg, F 67084, Strasbourg, France
    Methods Mol Biol 540:247-63. 2009
    ..Protocols to prepare the ribosome and the subunits are also given for Thermus thermophilus, Staphylococcus aureus, and Escherichia coli...
  43. pmc Contribution of 16S rRNA nucleotides forming the 30S subunit A and P sites to translation in Escherichia coli
    Nimo M Abdi
    Department of Microbiology, The Ohio State University, Columbus, 43210, USA
    RNA 11:1624-32. 2005
    ..In addition, we show that G1338A suppresses phenotypes conferred by m(2)G966A and several multiple P-site substitutions, suggesting that adenine at position 1338 can stabilize tRNA interaction in the P site...
  44. pmc Altered interactions between stem-loop IV within the 5' noncoding region of coxsackievirus RNA and poly(rC) binding protein 2: effects on IRES-mediated translation and viral infectivity
    Polen Sean
    Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA
    Virology 389:45-58. 2009
    ....
  45. pmc Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2
    K Asano
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
    EMBO J 18:1673-88. 1999
    ..Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2...
  46. pmc Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control
    J P Abastado
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
    Mol Cell Biol 11:486-96. 1991
    ..Under nonstarvation conditions, ribosomes would recover more rapidly from uORF1 translation, causing them all to reinitiate at uORF4 rather than at GCN4...
  47. pmc IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3'UTR
    Susan Weinlich
    Institute of Biochemistry and Biotechnology, Martin Luther University Halle Wittenberg, 06120 Halle Saale, Germany
    RNA 15:1528-42. 2009
    ..Our data suggest that IGF2BP1, by binding to the HCV 5'UTR and/or HCV 3'UTR, recruits eIF3 and enhances HCV IRES-mediated translation...
  48. pmc UNR translation can be driven by an IRES element that is negatively regulated by polypyrimidine tract binding protein
    Sigrid Cornelis
    Department for Molecular Biomedical Research, VIB Ghent University, Unit of Molecular Signal Transduction in Inflammation B 9052 Gent Zwijnaarde, Belgium
    Nucleic Acids Res 33:3095-108. 2005
    ..In conclusion, our results demonstrate that translation of the ITAF Unr can itself be regulated by an IRES that is downregulated by PTB...
  49. pmc A quantitative kinetic scheme for 70 S translation initiation complex formation
    Christina Grigoriadou
    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Mol Biol 373:562-72. 2007
    ..GDPCP does not affect stable 70 S formation, but perturbs fMet-tRNA(fMet) positioning in the P-site. In contrast, thiostrepton severely retards stable 70 S formation, but allows normal binding of fMet-tRNA(fMet)(prf20) to the P-site...
  50. ncbi Alternative translation start sites and hidden coding potential of eukaryotic mRNAs
    Alex V Kochetov
    Institute of Cytology and Genetics, Novosibirsk, Russia
    Bioessays 30:683-91. 2008
    ..The functional role of alternative translation and its contribution to eukaryotic proteome complexity are discussed...
  51. ncbi Multiple upstream AUG codons mediate translational control of GCN4
    P P Mueller
    Cell 45:201-7. 1986
    ..The interaction between the upstream AUG codons is modulated by the trans-acting factors GCN2 and GCD1 in response to amino acid availability...
  52. ncbi Ribosomal scanning on the highly structured insulin-like growth factor II-leader 1
    Alike W van der Velden
    Department of Developmental Biology, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands
    Int J Biochem Cell Biol 34:286-97. 2002
    ..As scanning seems unlikely, and internal entry and shunting were shown not to occur, we discuss a modified scanning mechanism for architecturally complex 5'UTRs...
  53. ncbi Lentiviral RNAs can use different mechanisms for translation initiation
    Emiliano P Ricci
    Unité de Virologie Humaine, Ecole Normale Superieure de Lyon, IFR 128, Lyon, F 69364, France
    Biochem Soc Trans 36:690-3. 2008
    ..Our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism...
  54. ncbi Kinetic checkpoint at a late step in translation initiation
    Pohl Milon
    Department of Biology MCA, Laboratory of Genetics, University of Camerino, 62032 Camerino, Italy
    Mol Cell 30:712-20. 2008
    ....
  55. ncbi Anticodon sequence mutants of Escherichia coli initiator tRNA: effects of overproduction of aminoacyl-tRNA synthetases, methionyl-tRNA formyltransferase, and initiation factor 2 on activity in initiation
    Christine Mayer
    Department of Biology, 68 671 Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Biochemistry 42:4787-99. 2003
    ..Other results suggest that the C1xA72 base pair mismatch, unique to eubacterial and organellar initiator tRNAs, may also be important for the binding of fAA-tRNA to IF2...
  56. pmc Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes
    J T Mendell
    Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Cell Biol 20:8944-57. 2000
    ..Based on these findings, a novel model in which Upf2p and rent2 effects decreased translation and accelerated decay of nonsense transcripts through competitive interactions with eIF4G-binding partners is proposed...
  57. ncbi The poly(A) binding protein is required for poly(A) shortening and 60S ribosomal subunit-dependent translation initiation
    A B Sachs
    Department of Biochemistry, Stanford University Medical Center, California 94305
    Cell 58:857-67. 1989
    ..These data suggest that the 60S subunit mediates the PAB requirement of translation initiation, thereby ensuring that only intact poly(A)+ mRNA will be translated efficiently in vivo...
  58. pmc Ribosomal protein S15 from Escherichia coli modulates its own translation by trapping the ribosome on the mRNA initiation loading site
    C Philippe
    Unité Propre de Recherche 9002 du Centre National de la Recherche Scientifique, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France
    Proc Natl Acad Sci U S A 90:4394-8. 1993
    ..Our results indicate that S15 prevents the formation of a functional ternary 30S-mRNA-tRNA(fMet) complex, the ribosome being trapped in a preternary 30S-mRNA-tRNA(fMet) complex...
  59. pmc The ribosome filter hypothesis
    Vincent P Mauro
    Department of Neurobiology, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:12031-6. 2002
    ..We propose that ribosomal filters may be important in cell differentiation and describe experimental tests for the filter hypothesis...
  60. pmc Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes
    M Kozak
    Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854
    Proc Natl Acad Sci U S A 87:8301-5. 1990
    ..This may be relevant to recent reports of adventitious upstream initiation events at non-AUG codons in some vertebrate mRNAs that have structure-prone, G + C-rich leader sequences...
  61. pmc Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution
    E Martinez-Salas
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Spain
    J Virol 70:992-8. 1996
    ..The results indicate a critical participation of the base of domain 3 in the activity of the aphthovirus IRES, with a strong effect of secondary or higher-order structures and minor effects of primary structure...
  62. pmc Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of mRNAs in Saccharomyces cerevisiae
    D C Schwartz
    Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA
    Mol Cell Biol 19:5247-56. 1999
    ..This view also implies that some cis-acting sequences that modulate mRNA decay rate do so by affecting the translation status of the transcript...
  63. pmc Ribosomal position and contacts of mRNA in eukaryotic translation initiation complexes
    Andrey V Pisarev
    Department of Microbiology and Immunology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
    EMBO J 27:1609-21. 2008
    ....
  64. ncbi Reduced but accurate translation from a mutant AUA initiation codon in the mitochondrial COX2 mRNA of Saccharomyces cerevisiae
    J J Mulero
    Section of Biochemistry, Molecular and Cell Biology Cornell University, Ithaca, NY 14853 2703
    Mol Gen Genet 242:383-90. 1994
    ....
  65. ncbi Recent mechanistic insights into eukaryotic ribosomes
    Marina V Rodnina
    Max Planck Institute for Biophysical Chemistry, Department of Physical Biochemistry, 37077 Gottingen, Germany
    Curr Opin Cell Biol 21:435-43. 2009
    ..Here, we summarize recent progress in deciphering molecular mechanisms of eukaryotic translation. Comparisons with prokaryotic translation are included, emphasizing emerging patterns of common design...
  66. ncbi mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events
    Marina K Holz
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 123:569-80. 2005
    ..Thus, the eIF3 preinitiation complex acts as a scaffold to coordinate a dynamic sequence of events in response to stimuli that promote efficient protein synthesis...
  67. ncbi Crystal structure of an RNA tertiary domain essential to HCV IRES-mediated translation initiation
    Jeffrey S Kieft
    1 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114 USA 2 Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520 8114 USA
    Nat Struct Biol 9:370-4. 2002
    ..This distorted stack probably serves as an important recognition surface for the translational machinery...
  68. pmc Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation
    Olga Fernandez-Miragall
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Cantoblanco, 28049 Madrid, Spain
    RNA 12:223-34. 2006
    ..Thus, we propose that the central domain of the FMDV IRES contains a structural conformation essential for IRES activity stabilized by a tertiary contact involving residues in the GNRA tetraloop and motif A conserved sequences...
  69. pmc The importance of inter- and intramolecular base pairing for translation reinitiation on a eukaryotic bicistronic mRNA
    Christine Luttermann
    Institut fur Immunologie, Friedrich Loeffler Institut, Tubingen, Germany
    Genes Dev 23:331-44. 2009
    ..Analysis of the essential elements of the TURBS led to a better understanding of the requirements for translation termination/reinitiation in eukaryotes...
  70. ncbi Structured mRNAs regulate translation initiation by binding to the platform of the ribosome
    Stefano Marzi
    IGBMC Institute of Genetics and of Molecular and Cellular Biology, Department of Structural Biology and Genomics, Illkirch, F 67404 France
    Cell 130:1019-31. 2007
    ..Different types of mRNA structures may be accommodated during translation preinitiation and regulate gene expression by transiently stalling the ribosome...
  71. pmc Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex
    Andrey V Pisarev
    Department of Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    Genes Dev 20:624-36. 2006
    ....
  72. pmc An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation
    Chingakham Ranjit Singh
    Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, 66506, USA
    EMBO J 25:4537-46. 2006
    ..We propose that the eIF2/eIF5 complex represents a cytoplasmic reservoir for eIF2 that antagonizes eIF2B-promoted guanine nucleotide exchange, enabling coordinated regulation of translation initiation...
  73. pmc eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange
    G D Pavitt
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
    Genes Dev 12:514-26. 1998
    ....
  74. ncbi AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context
    Alex V Kochetov
    Institute of Cytology and Genetics Lavrentieva 10, Novosibirsk 630090 Russia
    Bioinformatics 21:837-40. 2005
    ..It is likely that at least some mRNAs with suboptimal start codon context contain the other signals providing additional information for efficient AUG recognition...
  75. ncbi The joining of ribosomal subunits in eukaryotes requires eIF5B
    T V Pestova
    Department of Microbiology and Immunology, State University of New York Health Science Center at Brooklyn, 11203, USA
    Nature 403:332-5. 2000
    ..It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function...
  76. ncbi The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites
    Andrea Rivas-Aravena
    Instituto Milenio de Inmunología e Inmunoterapia, Jeune Equipe Associée à l IRD, Centro de Investigaciones Medicas, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Virology 392:178-85. 2009
    ..Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression...
  77. pmc The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene
    Yi Wen Kong
    School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom
    Proc Natl Acad Sci U S A 105:8866-71. 2008
    ..Overall, these data establish a link between the nuclear history of an mRNA and the mechanism of miRNA-mediated translational regulation in the cytoplasm...
  78. ncbi Inhibition of translational initiation by Let-7 MicroRNA in human cells
    Ramesh S Pillai
    Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
    Science 309:1573-6. 2005
    ..Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression...
  79. pmc Dendritic BC1 RNA: functional role in regulation of translation initiation
    Huidong Wang
    Department of Physiology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York 11203, USA
    J Neurosci 22:10232-41. 2002
    ..The results suggest a functional role of BC1 RNA as a mediator of translational control in local protein synthesis in nerve cells...
  80. pmc Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes
    T E Dever
    Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, Bethesda, Maryland 20892 2785, USA
    Mol Cell Biol 15:6351-63. 1995
    ..Met-tRNA(iMet) ternary complexes is the cardinal parameter determining the site of reinitiation on GCN4 mRNA and support the idea that reinitiation at GCN4 is inversely related to the concentration of ternary complexes in the cell...
  81. ncbi The molecular mechanics of eukaryotic translation
    Lee D Kapp
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205 2185, USA
    Annu Rev Biochem 73:657-704. 2004
    ..We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway...
  82. ncbi Dynamics and processivity of 40S ribosome scanning on mRNA in yeast
    Karine Berthelot
    Department of Biomolecular Sciences, UMIST, Manchester, UK
    Mol Microbiol 51:987-1001. 2004
    ..We have developed a biased bidirectional walking model of ribosomal scanning that provides a framework for understanding the above observations as well as other known quantitative and qualitative features of this process...
  83. pmc The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring upstream open reading frames
    Bijoyita Roy
    Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee 37996, USA
    RNA 16:748-61. 2010
    ..Together, these results attribute a specific molecular function in translation initiation to an individual eIF3 subunit in a multicellular eukaryote...
  84. ncbi A simplified reconstitution of mRNA-directed peptide synthesis: activity of the epsilon enhancer and an unnatural amino acid
    A C Forster
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    Anal Biochem 297:60-70. 2001
    ..The recombinant clones can be exploited to prepare initiation factors and initiation complexes for structural studies, to study initiation and elongation in ribosomal peptide synthesis, and to screen for eubacterial-specific drugs...
  85. pmc Mutation at position 791 in Escherichia coli 16S ribosomal RNA affects processes involved in the initiation of protein synthesis
    W E Tapprich
    Section of Biochemistry, Brown University, Providence RI 02912
    Proc Natl Acad Sci U S A 86:4927-31. 1989
    ....
  86. pmc The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH
    Ivan B Lomakin
    Department of Microbiology and Immunology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
    EMBO J 25:196-210. 2006
    ....
  87. ncbi Structure of the 30S translation initiation complex
    Angelita Simonetti
    Institute of Genetics and of Molecular and Cellular Biology, Department of Structural Biology and Genomics, Illkirch F 67404, France
    Nature 455:416-20. 2008
    ....
  88. ncbi Transient idling of posttermination ribosomes ready to reinitiate protein synthesis
    Andrey L Karamyshev
    Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Biochimie 86:933-8. 2004
    ....
  89. ncbi Regulation of translation initiation by RNA binding proteins
    Paul Babitzke
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Annu Rev Microbiol 63:27-44. 2009
    ..Examples also exist in which the bound protein traps the ribosome in a complex that is incapable of initiating translation...
  90. pmc Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site
    Alissa M Lancaster
    Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305, USA
    RNA 12:894-902. 2006
    ..This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA...
  91. pmc Picornavirus IRESes and the poly(A) tail jointly promote cap-independent translation in a mammalian cell-free system
    G Bergamini
    Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany
    RNA 6:1781-90. 2000
    ..The cell-free system described here should prove useful in studying these questions as well as providing a general biochemical tool to examine the translation initiation pathway in a more physiological setting...
  92. ncbi Translation reinitiation and leaky scanning in plant viruses
    Lyubov A Ryabova
    Institut de Biologie Moleculaire des Plantes, UPR CNRS 2357, Strasbourg, France
    Virus Res 119:52-62. 2006
    ..While internal initiation is treated in another section of this issue, we concentrate on leaky scanning, shunt and reinitiation, with emphasis on plant pararetroviruses...
  93. ncbi Identification and characterization of a novel cell cycle-regulated internal ribosome entry site
    S Cornelis
    Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Gent, Belgium
    Mol Cell 5:597-605. 2000
    ..The IRES element is localized to the mRNA coding region, and its activity is cell cycle regulated, which permits translation of p58(PITSLRE) in G2/M...
  94. pmc Ultrabithorax and Antennapedia 5' untranslated regions promote developmentally regulated internal translation initiation
    X Ye
    Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA
    Mol Cell Biol 17:1714-21. 1997
    ..Although the developmental patterns of expression directed by the Antp and Ubx IRESs overlap, they exhibit several differences indicating that these IRESs are not functionally equivalent...
  95. ncbi Function of eukaryotic initiation factor 5 in the formation of an 80 S ribosomal polypeptide chain initiation complex
    A Chakrabarti
    Department of Developmental Biology and Cancer, Albert Einstein College of Medicine, Bronx, New York 10461
    J Biol Chem 266:14039-45. 1991
    ..40 S.AUG.Met-tRNAf.eIF-2.GTP) eIF-5----(40 S.AUG.Met-tRNAf) + (eIF-2.GDP) + Pi (1) (40 S.AUG.Met-tRNAf) + 60 S----(80 S.AUG.Met-tRNAf) (2) 80 S initiation complex...
  96. pmc Role of methionine and formylation of initiator tRNA in initiation of protein synthesis in Escherichia coli
    U Varshney
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    J Bacteriol 174:7819-26. 1992
    ..Consequently, a subset of mutant tRNAs which are defective in formylation and therefore inactive in initiation when they are aminoacylated with glutamine become partially active when MetRS is overproduced...
  97. ncbi Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation
    B J Lamphear
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport 71130 3932, USA
    J Biol Chem 270:21975-83. 1995
    ..Only the latter would appear to be necessary for internal initiation of picornaviral RNAs...
  98. pmc Evidence for a role of initiation factor 3 in recycling of ribosomal complexes stalled on mRNAs in Escherichia coli
    N S Singh
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
    Nucleic Acids Res 33:5591-601. 2005
    ..coli EFG in vivo and in vitro. These lines of evidence clearly demonstrate the physiological importance of IF3 in the overall mechanism of ribosome recycling in E.coli...
  99. ncbi Ribosomal protein S5 interacts with the internal ribosomal entry site of hepatitis C virus
    S Fukushi
    Research and Development Center, BioMedical Laboratories, 1361 1 Matoba, Kawagoe, Saitama 350 1101, Japan
    J Biol Chem 276:20824-6. 2001
    ..Thus, our results support rpS5 as the critical element in positioning the HCV RNA on the 40 S ribosomal subunit during translation initiation...
  100. pmc Dissecting eukaryotic translation and its control by ribosome density mapping
    Yoav Arava
    Howard Hughes Medical Institute, Stanford, CA 94305 5428, USA
    Nucleic Acids Res 33:2421-32. 2005
    ..These results provide new insights into eukaryotic translation in vivo...
  101. ncbi Redundancy of non-AUG initiators. A clever mechanism to enhance the efficiency of translation in yeast
    Kuang Jung Chang
    Department of Life Science, National Central University, Jung li, 32001 Taiwan
    J Biol Chem 281:7775-83. 2006
    ..Cumulatively, the results suggest that this feature of redundancy of non-AUG initiators in a single mRNA per se may represent a novel paradigm for improving the efficiency of a poor or otherwise nonproductive initiation event...

Research Grants43

  1. TRANSLATIONAL CONTROL MEDIATED BY MRNA STRUCTURE
    Marilyn Kozak; Fiscal Year: 2002
    ..The reason why 40S ribosome/factor complexes protect "extra" sequences, which are accessible to RNase in 80S initiation complexes, will be studied. ..
  2. Small Molecule Effectors of Eukaryotic Translation Initiation Site Selection
    Jon Lorsch; Fiscal Year: 2008
    ..A deeper understanding of this complex cellular machine could lead to new approaches to treat the myriad diseases that affect the ribosome's function. [unreadable] [unreadable] [unreadable]..
  3. MYOCARDIAL PROTEIN SYNTHESIS AFTER ALCOHOL INTOXICATION
    Charles H Lang; Fiscal Year: 2010
    ..Overall, the research design will establish the mechanism by which myocardial protein synthesis is reduced in response to alcohol abuse. ..
  4. Myocardial Protein Synthesis After Thermal Injury
    Charles Lang; Fiscal Year: 2005
    ..Overall, the research will elucidate the mechanisms by which myocardial protein synthesis is reduced after thermal injury, leading to the better understanding and treatment of the resulting cardiomyopathy. - ..
  5. Antiretroviral-Induced Defects in Muscle Protein Synthesis
    Charles H Lang; Fiscal Year: 2010
    ..Such data is needed to both realize the full potential and avoid possible pitfalls of this drug in the long-term treatment of HIV-infected individuals. ..
  6. Alcohol-Induced Regulation of Hepatic Protein Synthesis
    THOMAS VARY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  7. Hantavirus RNA Encapsidation
    Antonito Panganiban; Fiscal Year: 2006
    ..abstract_text> ..
  8. Thickening of basement membrane in diabetic retinopathy
    Sayon Roy; Fiscal Year: 2007
    ..Findings from this project will establish or exclude a pathogenetic link between a discrete biosynthetic abnormality and the development of structural and functional lesions of diabetic retinopathy. ..
  9. Role of p170 in lung tumorigenesis
    Jian Ting Zhang; Fiscal Year: 2007
    ..This work will certainly add to our understanding of the functional mechanism of translation initiation of protein synthesis. ..
  10. HNF-4 and coactivators in apoAl gene regulation
    Sohail Malik; Fiscal Year: 2008
    ..They will also potentially reveal targets for future therapeutic developments in the metabolic and cardiovascular areas. [unreadable] [unreadable]..
  11. Development of tools for structural genomics of viral RNA
    JEFFREY KIEFT; Fiscal Year: 2008
    ..By solving the structures of these RNAs, we will inform and enable new strategies for developing therapeutics aimed at curing viral disease. [unreadable] [unreadable] [unreadable]..
  12. Molecular Biology of Erythrocyte Ankyrin
    Patrick G Gallagher; Fiscal Year: 2010
    ..These studies may provide important information to be used for diagnosis and treatment of patients with this disorder. ..
  13. Functions of Double-stranded RNA Binding Proteins
    Michael Mathews; Fiscal Year: 2008
    ..3. Protein complexes formed by NF90 isoforms and the changes brought about by viral infection, interferon treatment, and cell cycle block. 4. The functions of NF90 isoforms during infection with adenovirus and HIV. ..
  14. Structure and Function of the Hepatitis C Virus Genome
    PETER contact SARNOW; Fiscal Year: 2010
    ..To do this, novel biochemical, structural and genetic approaches will be employed to study protein-HCV RNA interactions. ..
  15. MECHANISM OF TRP GENE REGULATION BY TRAP-RNA RECOGNITION
    Paul Babitzke; Fiscal Year: 2009
    ..Genetic and biochemical experiments will be carried out to understand how the relative placement of the triplet repeats influences TRAP-mediated translation control of these three genes. ..
  16. Roles for RCK/DDX6 in hepatitis C virus pathogenesis and hepatocellular carcinoma
    Peter Sarnow; Fiscal Year: 2010
    ..abstract_text> ..
  17. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  18. Regulation of translation initiation in eukaryotes
    Vincent P Mauro; Fiscal Year: 2010
    ..g. for the production of therapeutic proteins, and new avenues for analyzing the potential contributions of mis-regulation to disease. ..
  19. Translational Control of Retroviral Unspliced mRNA
    KATHLEEN A BORIS LAWRIE; Fiscal Year: 2010
    ..abstract_text> ..
  20. Cell Type-Specific Viral Translation in the CNS
    Matthias Gromeier; Fiscal Year: 2006
    ..This principle has shown great promise in pre-clinical studies in experimental animals and in primary explant cultures of human CNS tumors. ..
  21. Translational control by microRNAs
    Peter Sarnow; Fiscal Year: 2006
    ..The health-relatedness of this project lies in the potential roles of this novel mechanism of gene regulation in cell growth or development. ..
  22. REGULATION OF HIV1 GENE EXPRESSION BY TAT AND TAR
    Michael Mathews; Fiscal Year: 2001
    ..In addition, we propose to identify and study factor(s) responsible for potentiating Tat's ability to stimulate HIV-1 directed transcription in a cell-free system. ..
  23. MOLECULAR BASES OF MULTIDRUG RESISTANCE IN CANCERS
    Jian Ting Zhang; Fiscal Year: 2001
    ..Additionally, this study will increase our understanding of how specific protein topological structures are related to transport functions in general. ..
  24. Integrated LC/MS/MS System
    Michael Mathews; Fiscal Year: 2002
    ..The addition of the integrated ThermoFinnigan LCQ DECA-10000/LC Packings Ultimate LC/MC/MS system will complement our existing MALDI-TOF instrument, permitting the facility to cover most of our mass spectrometry needs. ..
  25. BASEMENT MEMBRANE THICKENING IN DIABETIC RETINOPATHY
    Sayon Roy; Fiscal Year: 2002
    ..A successful study would provide the critical information that inhibition of excess synthesis of basement membranes prevents background diabetic retinopathy. ..
  26. HIV-1 RNA ENCAPSIDATION, DIMER FORMATION, AND STRUCTURE
    Antonito Panganiban; Fiscal Year: 2002
    ..We hope to develop a comprehensive picture that helps us understand in and exact way how correct encapsidation and dimer formation lead to correct reverse transcription. ..
  27. STRUCTURE/FUNCTION OF PICORNAVIRUS RNA GENOMES
    Peter Sarnow; Fiscal Year: 2002
    ..Cells that have functionally inactivated allelic loci and that are resistant to infection by either picornavirus or rhinovirus will be selected and the disrupted genes will be identified and characterized in detail. ..
  28. Translational regulation in Alzheimer's Disease
    Leslie Krushel; Fiscal Year: 2002
    ..The results will provide novel insights into the etiology of AD and present new avenues to explore for therapeutic intervention of individuals with AD or other vascular dementias. ..
  29. IN VITRO EVOLUTION OF NEW MOLECULAR FUNCTIONS
    Jack Szostak; Fiscal Year: 2003
    ..The re-use of previously selected functions to evolve new functions will also be studied. The idea that proteins are better than RNA at evolving new functions from existing functions will also be tested. ..
  30. INITIATION OF HEPATITIS C VIRUS TRANSLATION
    CHRISTOPHER HELLEN; Fiscal Year: 2001
    ..abstract_text> ..
  31. Mechanism of ribosomal subunit joining in eukaryotes
    Tatyana Pestova; Fiscal Year: 2005
    ....
  32. TRANSLATIONAL INITIATION IN EUKARYOTIC MRNA MOLECULES
    Peter Sarnow; Fiscal Year: 2005
    ..It is predicted that this unusual translation initiation pathway may operate when cells encounter a variety of stress situations, such as viral infection, heat shock, nutritional deprivation and hypoxia. ..
  33. Role of Vpu in HIV1 Particle Exit
    Antonito Panganiban; Fiscal Year: 2004
    ..Additional genetic experiments will be carried out to determine the nature of second site revertants that arise following the propagation of primary Vpu mutants. ..
  34. Internal Initiation in the Translation of Cellular mRNAs
    Vincent Mauro; Fiscal Year: 2004
    ....
  35. Genetically stable Picornavirus HIV Immunization vector
    Matthias Gromeier; Fiscal Year: 2004
    ..We will pursue to identify favorable structural characteristics leading to insert retention and efficient expression in our vectors to prepare them for HIV immunization studies in non-human primates. ..
  36. Automated Macromolecular Crystallization System
    JEFFREY KIEFT; Fiscal Year: 2007
    ..Cost savings. Cost of crystallization trials will decrease due to the use of smaller amounts of reagents, including solutions and protein/RNA samples. [unreadable] [unreadable] [unreadable]..
  37. Targeting the oligomerization of human ABCG2
    Jian Ting Zhang; Fiscal Year: 2009
    ..This work may also lead us to the discovery of a new class of therapeutic agents that can help overcome drug-resistant cancers. ..
  38. MECHANISM OF DRUG BINDING TO P-GLYCOPROTEIN
    Jian Ting Zhang; Fiscal Year: 2001
    ..This work may lead us to the discovery of a new family of chaperone proteins associated with ribosomes that are important in determining the folding of membrane proteins co-translationally. ..
  39. DRUG DISCOVERY BY MIRROR IMAGE LIGAND DISPLAY
    ANTHONY FORSTER; Fiscal Year: 2003
    ..3. To apply this strategy for drug discovery to other potential therapeutic targets, including the gp41 subunit of the HIV envelope glycoprotein and the breast-cancer specific, cell- surface glycoprotein MUC1. ..
  40. Translational control of LTP
    EMMANUEL LANDAU; Fiscal Year: 2007
    ..The results of this proposal will shed light on the mechanisms that participate in drug addiction, as well as learning and memory, by providing new information on the role of translation control in neuronal plasticity. ..
  41. CHIMERISM IN CORD BLOOD TRANSPLANTATION IN MICE
    Rona Weinberg; Fiscal Year: 2004
    ..These "pre-translational" studies form the basis for developing effective human CB transplantation and autologous CB gene therapy protocols. ..
  42. Functions of Spt4-Spt5 in Gene Expression
    Grant Hartzog; Fiscal Year: 2008
    ..Studies here include biochemical and genetic analyses of splicing in spt mutants and tests of the influence of Spt4-Spt5 on the assembly of RNA export proteins onto mRNA. ..