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Genomes and Genes | u1 small nuclear ribonucleoproteinSummarySummary: A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U1 snRNP along with other small nuclear ribonucleoproteins (U2, U4-U6, and U5) assemble into SPLICEOSOMES that remove introns from pre-mRNA by splicing. The U1 snRNA forms base pairs with conserved sequence motifs at the 5'-splice site and recognizes both the 5'- and 3'-splice sites and may have a fundamental role in aligning the two sites for the splicing reaction. Top Publications
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Publications
An RNA map predicting Nova-dependent splicing regulationJernej Ule
Howard Hughes Medical Institute, New York, New York 10021, USA
Nature 444:580-6. 2006....
Heterogeneous nuclear ribonucleoproteins H and F regulate the proteolipid protein/DM20 ratio by recruiting U1 small nuclear ribonucleoprotein through a complex array of G runsErming Wang
Department of Neurology, University of Kentucky, Lexington, Kentucky 40536, USA
J Biol Chem 284:11194-204. 2009..Binding of U1 small nuclear ribonucleoprotein (U1snRNP) to DM20 is greatly impaired by mutation of G1 and M2 and depletion of hnRNPH and F...
In vitro reconstitution of mammalian U1 snRNPs active in splicing: the U1-C protein enhances the formation of early (E) spliceosomal complexesC L Will
Institut fur Molekularbiologie und Tumorforschung, Philipps Universitat Marburg, Germany
Nucleic Acids Res 24:4614-23. 1996..Studies with recombinant U1-C protein mutants indicated that the N-terminal domain of U1-C is necessary and sufficient for the stimulation of E complex formation...
The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicingP Förch
Gene Expression Programme European Molecular Biology Laboratory Meyerhofstrasse 1 D 69117, Heidelberg, Germany
Mol Cell 6:1089-98. 2000....
Interaction of the U1 snRNP with nonconserved intronic sequences affects 5' splice site selectionO Puig
Gene Expression Program, European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
Genes Dev 13:569-80. 1999..This supports a model where early 5' splice recognition results from a network of interactions established by the splicing machinery with various regions of the pre-mRNA...
Sequence-specific interaction of U1 snRNA with the SMN complexJeongsik Yong
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA
EMBO J 21:1188-96. 2002..These findings indicate that SMN complex interaction with SL1 is sequence-specific and critical for U1 snRNP biogenesis, further supporting the direct role of the SMN complex in RNP biogenesis...
The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A proteinL Varani
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
Nat Struct Biol 7:329-35. 2000..This mechanism ensures that the activity of PAP enzyme, which is essential to the cell, is only down regulated when U1A is bound to the U1A mRNA...
The fate of U1 snRNP during anti-Fas induced apoptosis: specific cleavage of the U1 snRNA moleculeW G Degen
Department of Biochemistry, University of Nijmegen, NL 6500 HB Nijmegen, The Netherlands
Cell Death Differ 7:70-9. 2000....
The U1 snRNP base pairs with the 5' splice site within a penta-snRNP complexHadar Malca
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel
Mol Cell Biol 23:3442-55. 2003..This fraction is functional in mRNA spliceosome assembly when supplemented with soluble nuclear proteins. The results argue that U1 can bind the 5' splice site in a mammalian preassembled penta-snRNP complex...
An SC35-like protein and a novel serine/arginine-rich protein interact with Arabidopsis U1-70K proteinM Golovkin
Department of Biology and Program in Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, USA
J Biol Chem 274:36428-38. 1999The U1 small nuclear ribonucleoprotein 70-kDa protein, a U1 small nuclear ribonucleoprotein-specific protein, has been shown to have multiple roles in nuclear precursor mRNA processing in animals...
Altering the RNA-binding mode of the U1A RBD1 proteinScott A Showalter
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
J Mol Biol 335:465-80. 2004..The molecular basis for this alteration in RNA-binding properties is proposed to result from the inability of the RNA to induce a change in the structure of the free protein to produce a high-affinity complex...
Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP additionS Chung
T H Morgan School of Biological Sciences and The Markey Cancer Center, University of Kentucky, Lexington 40506 0225, USA
RNA 5:1042-54. 1999..Our results indicate that Clf1p acts as a scaffolding protein in spliceosome assembly and suggest that Clf1p may support the cross-intron bridge during the prespliceosome-to-spliceosome transition...
Dephosphorylated SRp38 acts as a splicing repressor in response to heat shockChanseok Shin
Department of Biological Sciences, Columbia University, New York, New York 10027, USA
Nature 427:553-8. 2004..We further show that dephosphorylated SRp38 interacts with a U1 small nuclear ribonucleoprotein particle (snRNP) protein, and that this interaction interferes with 5'-splice-site recognition by ..
An intronic polypyrimidine-rich element downstream of the donor site modulates cystic fibrosis transmembrane conductance regulator exon 9 alternative splicingElisabetta Zuccato
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste 34012, Italy
J Biol Chem 279:16980-8. 2004..exon 9 inclusion, consistent with the facilitating role of TIA-1 in weak 5'-ss recognition by U1 small nuclear ribonucleoprotein. Interestingly, in the presence of a high number of TG repeats and a low number of T repeats in the ..
Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the U1snRNP associated U1C protein; epitope mapping, immunolocalization and V-gene usageR M Hoet
Department of Biochemistry, University of Nijmegen, The Netherlands
Mol Immunol 35:1045-55. 1998..The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure...
The yeast splicing factor Prp40p contains functional leucine-rich nuclear export signals that are essential for splicingMark W Murphy
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
Genetics 166:53-65. 2004....
Crystal structure of the spliceosomal U2B"-U2A' protein complex bound to a fragment of U2 small nuclear RNAS R Price
MRC Laboratory of Molecular Biology, Cambridge, UK
Nature 394:645-50. 1998....
A serine/arginine-rich domain in the human U1 70k protein is necessary and sufficient for ASF/SF2 bindingW Cao
Department of Pharmacology and Cancer Biology, Levine Science Research Center, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 273:20629-35. 1998..ASF/SF2, SC35, and other members of the serine/arginine family, interact with the 70k protein of the U1 small nuclear ribonucleoprotein. The binding of this protein with ASF/SF2 is thought to enhance recognition of the 5' splice site of ..
Nuclear accumulation of the U1 snRNP-specific protein C is due to diffusion and retention in the nucleusJ M Klein Gunnewiek
Department of Biochemistry, University of Nijmegen, Nijmegen, 6500 HB, The Netherlands
Exp Cell Res 235:265-73. 1997The U1 small nuclear ribonucleoprotein particle (snRNP) has an important function in the early formation of the spliceosome, the multicomponent complex in which pre-mRNA splicing takes place...
A functional role for correlated motion in the N-terminal RNA-binding domain of human U1A proteinScott A Showalter
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid, Box 8231, 63110, St Louis, MO, USA
J Mol Biol 322:533-42. 2002..Interpretation of the novel RED results and corresponding NMR relaxation data suggests that the loss of collective motions in the mutants could account for their weak RNA-binding...
Determinants within an 18-amino-acid U1A autoregulatory domain that uncouple cooperative RNA binding, inhibition of polyadenylation, and homodimerizationFei Guan
Rutgers University, Piscataway, New Jersey 08854, USA
Mol Cell Biol 23:3163-72. 2003..Our molecular dissection of the consequences of conformational changes within an RNP complex presents a powerful example to those studying more complicated pre-mRNA-regulatory systems...
Antinuclear antibodies recognize cellular autoantigens driven by apoptosisRoxana Ramírez-Sandoval
Department of Molecular Biology, Centro de Biología Experimental, Universidad Autonoma de Zacatecas, Chepinque 306, Col Lomas de la Soledad, 98040, Zacatecas, Mexico
Joint Bone Spine 70:187-94. 2003..Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis...
An intronic splicing enhancer binds U1 snRNPs to enhance splicing and select 5' splice sitesA J McCullough
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
Mol Cell Biol 20:9225-35. 2000..We suggest that the G-rich region near vertebrate 5' splice sites promotes accurate splice site recognition by recruiting the U1 snRNP...
The fate of the U1 snRNP autoantigen during apoptosis: implications for systemic autoimmunityKelen C R Malmegrim
Department of Biochemistry, Nijmegen Center of Molecular Life Sciences, University of Nijmegen, Nijmegen, The Netherlands
Isr Med Assoc J 4:706-12. 2002....
A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPsG Meister
Max-Planck Institute of Biochemistry, Am Klopferspitz 18a, D-82152 Martinsried, Germany
Nat Cell Biol 3:945-9. 2001..These data provide the first direct evidence that a complex containing SMN and Gemin2 mediates the active assembly of spliceosomal U snRNPs...
Secondary necrosis is a source of proteolytically modified forms of specific intracellular autoantigens: implications for systemic autoimmunityX Wu
Loma Linda University School of Medicine, California, USA
Arthritis Rheum 44:2642-52. 2001....
Substitution of an essential adenine in the U1A-RNA complex with a non-polar isostereJacob B Tuite
Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA
Nucleic Acids Res 30:5269-75. 2002..The data imply that hydrophobic interactions can compensate energetically for the disruption of the complex hydrogen-bonding network between nucleotide and protein...
The Drosophila U2 snRNP protein U2A' has an essential function that is SNF/U2B" independentA A Nagengast
Department of Genetics, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106 4955, USA
Nucleic Acids Res 29:3841-7. 2001..Thus together these data demonstrate that in Drosophila U2A' has an essential function that is unrelated to its role as the partner protein of SNF/U2B"...
Modulation of P-element pre-mRNA splicing by a direct interaction between PSI and U1 snRNP 70K proteinE Labourier
Department of Molecular and Cell Biology, University of California, Berkeley, 401 Barker Hall 3204, Berkeley, CA 94720, USA
Mol Cell 8:363-73. 2001..Here we have identified a direct association of PSI with the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle in somatic nuclear extracts...
Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infectionM M Newkirk
Division of Rheumatology, The Montreal General Hospital, McGill University, Montreal, Quebec, Canada
Arthritis Res 3:253-8. 2001The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood...
Spliceosomal UsnRNP biogenesis, structure and functionC L Will
Max Planck Institute of Biophysical Chemistry, Department of Cellular Biochemistry, Am Fassberg 11, 37077 Gottingen, Germany
Curr Opin Cell Biol 13:290-301. 2001....
A general role for splicing enhancers in exon definitionBianca J Lam
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92697-4025, USA
RNA 8:1233-41. 2002..Our results suggest that ESEs recruit a multicomponent complex that minimally contains components of the splicing machinery required for 5' and 3' splice site selection...
The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kd and B'/B proteins as predominant U1 RNP immunogensE L Greidinger
University of Missouri, Columbia, USA
Arthritis Rheum 44:368-75. 2001..CONCLUSION: Orderly patterns of emergence of U1 RNP peptide antibodies appear to exist in humans. Two peptides, 70 kd and B'/B, show characteristics of early immunogens in the development of human RNP immunity...
Sm protein-Sm site RNA interactions within the inner ring of the spliceosomal snRNP core structureH Urlaub
Max Planck Institute of Biophysical Chemistry, Department of Cellular Biochemistry, Am Fassberg 11, D 37077 Gottingen, Germany
EMBO J 20:187-96. 2001..Our results thus provide the first evidence that, within the core snRNP, multiple Sm protein-Sm site RNA contacts occur on the inner surface of the heptameric Sm protein ring...
Yeast U1 snRNP-pre-mRNA complex formation without U1snRNA-pre-mRNA base pairingH Du
Department of Biology, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
RNA 7:133-42. 2001..Only one of these is base pairing between the 5' splice site and the 5' end of U1 snRNA, without which the U1 snRNP-pre-mRNA complex is less stable and has a somewhat altered conformation...
Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD box splicing factorJ Y Chen
Department of Molecular Genetics, Ohio State University, Columbus, OH 43210, USA
Mol Cell 7:227-32. 2001..to counteract the stabilizing effect of the U1-C protein, thereby promoting the dissociation of the U1 small nuclear ribonucleoprotein particle from the 5' splice site...
Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skippingAlexis A Nagengast
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106 4955, USA
Development 130:463-71. 2003....
Apoptotic U1-70 kd is antigenically distinct from the intact form of the U1-70-kd moleculeEric L Greidinger
University of Missouri and Department of Veterans Affairs Medical Research Service, Harry S Truman Memorial Veterans Hospital, Columbia, Missouri, USA
Arthritis Rheum 46:1264-9. 2002..To determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen...
U1A inhibits cleavage at the immunoglobulin M heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regionsCatherine Phillips
Molecular Biology and Biochemistry, Rutgers University, Nelson Labs, Room A322, 604 Allison Rd, Piscataway, NJ 08854, USA
Mol Cell Biol 24:6162-71. 2004..We demonstrate here that U1A binds two (AUGCN(1-3)C) motifs within the 29-nucleotide sequence and inhibits the binding of cleavage stimulatory factor 64K and cleavage at the secretory poly(A) site...
Structure and expression of a plant U1 snRNP 70K gene: alternative splicing of U1 snRNP 70K pre-mRNAs produces two different transcriptsM Golovkin
Department of Biology, Colorado State University, Fort Collins 80523, USA
Plant Cell 8:1421-35. 1996The product of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) 70K (U1-70K) gene, a U1 snRNP-specific protein, has been implicated in basic as well as alternative splicing of pre-mRNAs in animals...
Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursorsJ D Kohtz
Department of Biological Sciences, Columbia University, New York, New York 10027
Nature 368:119-24. 1994..This cooperation is probably achieved by specific interactions between the arginine/serine-rich domain of the splicing factor and a similar region in a U1 snRNP-specific protein...
The association of the U1-specific 70K and C proteins with U1 snRNPs is mediated in part by common U snRNP proteinsR L Nelissen
Department of Biochemistry, University of Nijmegen, The Netherlands
EMBO J 13:4113-25. 1994The U1 small nuclear ribonucleoprotein particle (snRNP)-specific 70K and A proteins are known to bind directly to stem-loops of the U1 snRNA, whereas the U1-C protein does not bind to naked U1 snRNA, but depends on other U1 snRNP protein ..
Molecular characterization of the spliceosomal proteins U1A and U2B" from higher plantsG G Simpson
Cell and Molecular Genetics Department, Scottish Crop Research Institute, Invergowrie, Dundee, UK
EMBO J 14:4540-50. 1995....
Complete MALDI-ToF MS analysis of cross-linked peptide-RNA oligonucleotides derived from nonlabeled UV-irradiated ribonucleoprotein particlesEva Kühn-Hölsken
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany
RNA 11:1915-30. 2005..This type of analysis is applicable to any type of RNP complex and may be expected to pave the way for the further analysis of protein-RNA complexes in much lower abundance and/or of cross-links that are obtained in low yield...
Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpinC Oubridge
MRC Laboratory of Molecular Biology, Cambridge, UK
Nature 372:432-8. 1994..The structure reveals the stereochemical basis for sequence-specific RNA recognition by the RNP domain...
The Drosophila sex determination gene snf encodes a nuclear protein with sequence and functional similarity to the mammalian U1A snRNP proteinT W Flickinger
Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106 4955
Genes Dev 8:914-25. 1994..These studies provide the first demonstration, in a multicellular organism, that mutations in a U1 snRNP protein alter splicing in vivo...
Nucleo-cytoplasmic transport of U snRNPs: definition of a nuclear location signal in the Sm core domain that binds a transport receptor independently of the m3G capU Fischer
, , Germany
EMBO J 12:573-83. 1993..We propose that the RNA structure of a given snRNP particle determines at least in part whether the particle's m3G cap is required for nuclear transport or can be dispensed with...
Structural basis for RanGTP independent entry of spliceosomal U snRNPs into the nucleusDaniel Wohlwend
Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik and GZMB, Georg August Universitat Gottingen, Justus von Liebig Weg 11, D 37077 Gottingen, Germany
J Mol Biol 374:1129-38. 2007....
A new type of mutation causes a splicing defect in ATMFranco Pagani
Molecular Pathology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
Nat Genet 30:426-9. 2002..a new intron-splicing processing element (ISPE) complementary to U1 snRNA, the RNA component of the U1 small nuclear ribonucleoprotein (snRNP)...
Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repressionJianglin Ma
Rutgers University, Department of Molecular Biology and Biochemistry, Nelson Laboratories, Room A322, 604 Allison Road, Piscataway, NJ 08854, USA
RNA 12:122-32. 2006....
A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigenEric L Greidinger
Division of Rheumatology and Immunology, University of Miami, Miami, Florida 33136, USA
Arthritis Rheum 54:661-9. 2006..To test whether immunizing mice with autoantigens closely linked to mixed connective tissue disease (MCTD) could induce an MCTD-like clinical syndrome distinguishable from systemic lupus erythematosus (SLE)...
Proteomic analysis of the U1 snRNP of Schizosaccharomyces pombe reveals three essential organism-specific proteinsAlain N S Newo
Institute of Genetics, Technical University of Braunschweig, Spielmannstr 7, 38106 Braunschweig, Germany
Nucleic Acids Res 35:1391-401. 2007..pombe are essential for growth. We will discuss the differences between the U1 snRNPs with respect to the organism-specific proteins found in the two yeasts and the resulting effect it has on pre-mRNA splicing...
Isolation of S. cerevisiae snRNPs: comparison of U1 and U4/U6.U5 to their human counterpartsP Fabrizio
Institut fur Molekularbiologie und Tumorforschung, Phillipps Universität, Marburg, Germany
Science 264:261-5. 1994..U5 snRNPs are significantly similar. The preparative isolation of yeast snRNPs will allow the cloning as well as genetic and phylogenetic analysis of snRNP proteins which will accelerate our understanding of their function...
Commitment of yeast pre-mRNA to the splicing pathway requires a novel U1 small nuclear ribonucleoprotein polypeptide, Prp39pS R Lockhart
T H Morgan School of Biological Sciences, University of Kentucky, Lexington 40506 0225
Mol Cell Biol 14:3623-33. 1994The binding of a U1 small nuclear ribonucleoprotein (snRNP) particle to the 5' splice site region of a pre-mRNA is a primary step of intron recognition...
Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigenD Hof
Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands
Autoimmun Rev 4:380-8. 2005....
hnRNP H binding at the 5' splice site correlates with the pathological effect of two intronic mutations in the NF-1 and TSHbeta genesEmanuele Buratti
International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy
Nucleic Acids Res 32:4224-36. 2004..Depletion analyses shows that this protein restricts the accessibility of U1 small nuclear ribonucleoprotein (U1snRNA) to the donor site...
Assembly and localization of the U1-specific snRNP C protein in the amphibian oocyteM F Jantsch
Department of Embryology, Carnegie Institution, Baltimore, Maryland 21210
J Cell Biol 119:1037-46. 1992..In transfected tissue culture cells, the myc-tagged C protein localized within the nucleus in a speckled pattern similar to that of endogenous U1 snRNPs...
Co-localisation studies of Arabidopsis SR splicing factors reveal different types of speckles in plant cell nucleiZdravko J Lorkovic
Max F Perutz Laboratories, Medical University of Vienna, Department of Medical Biochemistry, Vienna, Austria
Exp Cell Res 314:3175-86. 2008....
Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue diseaseDanielle Hof
Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands
Arthritis Res Ther 7:R302-9. 2005..Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most ..
U1 small nuclear RNP from Trypanosoma brucei: a minimal U1 snRNA with unusual protein componentsZsofia Palfi
, , D-35392 Giessen, Germany
Nucleic Acids Res 33:2493-503. 2005..These data result in a model of the trypanosome U1 snRNP, which deviates substantially from our classical view of the U1 particle and may reflect the special requirements for splicing of a small set of cis-introns in trypanosomes...
Solution structure of the N-terminal RNP domain of U1A protein: the role of C-terminal residues in structure stability and RNA bindingJ M Avis
MRC Laboratory of Molecular Biology, Cambridge, UK
J Mol Biol 257:398-411. 1996..The movement of helix C mainly involves changes in the main-chain torsion angles of Thr89, Asp90 and Ser91, the helix thereby acting as a "lid" over the RNA binding surface...
A study of collective atomic fluctuations and cooperativity in the U1A-RNA complex based on molecular dynamics simulationsBethany L Kormos
Chemistry Department and Molecular Biophysics Program, Wesleyan University, 237 Church St, Middletown, CT 06459, USA
J Struct Biol 157:500-13. 2007..This method has significant implications as a predictive tool regarding cooperativity in the protein-nucleic acid recognition process...
Hu antigen R (HuR) functions as an alternative pre-mRNA splicing regulator of Fas apoptosis-promoting receptor on exon definitionJosé M Izquierdo
Departamento de Biología Molecular and the Centro de Biología Molecular Severo Ochoa, C S I C, Universidad Autonoma de Madrid, Cantoblanco 28049, Madrid, Spain
J Biol Chem 283:19077-84. 2008..Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death...
Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcriptsSnehal Bhikhu Patel
Department of Biochemistry, College of Medicine, School of Molecular and Cellular Biology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
J Cell Biol 178:937-49. 2007..Collectively, these data indicate that the recruitment of snRNPs to nascent transcripts and the assembly of the spliceosome are uncoupled events...
SR proteins function in coupling RNAP II transcription to pre-mRNA splicingRita Das
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
Mol Cell 26:867-81. 2007..Thus, these factors readily out-compete inhibitory hnRNP proteins, resulting in efficient spliceosome assembly on nascent RNAP II transcripts...
Molecular dynamics simulation studies of induced fit and conformational capture in U1A-RNA binding: do molecular substates code for specificity?Felicia Pitici
Chemistry Department and Molecular Biophysics Program, Wesleyan University, Middletown, CT 06459, USA
Biopolymers 65:424-35. 2002..7947-7956) and by Williamson (Nature Structural Biology, 2000, Vol. 7, pp. 834-837) suggest an important role for intrinsic molecular architecture and substates other than the native form in the specificity of protein-RNA interactions...
Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activatorYing Feng
Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 10027, USA
Nat Struct Mol Biol 15:1040-8. 2008..Together, our data demonstrate that SRp38, in addition to its role as a splicing repressor, can function as an unusual sequence-specific splicing activator...
The splicing regulator TIA-1 interacts with U1-C to promote U1 snRNP recruitment to 5' splice sitesPatrik Förch
Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
EMBO J 21:6882-92. 2002The U1 small nuclear ribonucleoprotein (U1 snRNP) binds to the pre-mRNA 5' splice site (ss) at early stages of spliceosome assembly...
Prediction of salt and mutational effects on the association rate of U1A protein and U1 small nuclear RNA stem/loop IISanbo Qin
Department of Physics and Institute of Molecular Biophysics and School of Computational Science, Florida State University, Tallahassee, Florida 32306, USA
J Phys Chem B 112:5955-60. 2008..These observations are rationalized. Moreover, predicted effects of salt and charge mutations are found to be in quantitative agreement with experimental results...
T cell immunity in connective tissue disease patients targets the RNA binding domain of the U1-70kDa small nuclear ribonucleoproteinEric L Greidinger
Division of Immunology and Rheumatology, University of Missouri, Columbia, MO 65212, USA
J Immunol 169:3429-37. 2002..The T cell autoimmune response to U1-70kDa appears to have less diversity than is seen in the humoral response; and therefore, may be a favorable target for therapeutic intervention...
Snu56p is required for Mer1p-activated meiotic splicingRichard J Balzer
Department of Molecular Biology, UMNDJ SOM, 2 Medical Center Drive, Stratford, NJ 08084, USA
Mol Cell Biol 28:2497-508. 2008..Interestingly, these two proteins do not interact, suggesting that Snu56p links pre-mRNA-bound Mer1p to Nam8p in the U1 snRNP. This work demonstrates that the Snu56 protein is required for splicing only during meiosis...
Identification of nuclear spliceosomal antigens targeted by NOD mouse antibodies following sodium iodide intakeC Thompson
University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge, CB2 1QP, UK
Autoimmunity 39:99-106. 2006..The autoantibody isotypes most consistently represented were IgG2a and IgG2b...
A bidirectional SF2/ASF- and SRp40-dependent splicing enhancer regulates human immunodeficiency virus type 1 rev, env, vpu, and nef gene expressionMassimo Caputi
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA
J Virol 78:6517-26. 2004..4, even when the 5' splice site and the U1 snRNA have been mutated to obtain a perfect complementary match. The ESE characterized here is highly conserved in most viral subtypes...
Characterization of a U2AF-independent commitment complex (E') in the mammalian spliceosome assembly pathwayOliver A Kent
4-39 Medical Sciences Building, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
Mol Cell Biol 25:233-40. 2005..recognition of pre-mRNA during spliceosome assembly in mammals proceeds through the association of U1 small nuclear ribonucleoprotein particle (snRNP) with the 5' splice site as well as the interactions of the branch binding protein ..
Use of fluorescent protein tags to study nuclear organization of the spliceosomal machinery in transiently transformed living plant cellsZdravko J Lorkovic
Max F Perutz Laboratories, University Departments at the Vienna Biocenter, Institute of Medical Biochemistry, 1030 Vienna, Austria
Mol Biol Cell 15:3233-43. 2004....
Kinetic analysis of the role of the tyrosine 13, phenylalanine 56 and glutamine 54 network in the U1A/U1 hairpin II interactionMichael J Law
Department of Biochemistry and Molecular Biology, University of Southern California Los Angeles, CA 90089-9176, USA
Nucleic Acids Res 33:2917-28. 2005The A protein of the U1 small nuclear ribonucleoprotein particle, interacting with its stem-loop RNA target (U1hpII), is frequently used as a paradigm for RNA binding by recognition motif domains (RRMs)...
NSSRs/TASRs/SRp38s function as splicing modulators via binding to pre-mRNAsKazuo Fushimi
Center for Nano Materials and Technology, Japan Advanced Institute of Science and Technology, Nomi City, Ishikawa 923 1292, Japan
Genes Cells 10:531-41. 2005..5, all containing undifferentiated neural stem cells. Taken together, our results showed that NSSRs modulate alternative splicing via binding to premRNAs during neural differentiation...
Structural availability influences the capacity of autoantigenic epitopes to induce a widespread lupus-like autoimmune responseMicah T McClain
Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA
Proc Natl Acad Sci U S A 101:3551-6. 2004....
Mer1p is a modular splicing factor whose function depends on the conserved U2 snRNP protein Snu17pMarc Spingola
Center for the Molecular Biology of RNA, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
Nucleic Acids Res 32:1242-50. 2004..We conclude that Mer1p is a modular splicing regulator that can activate splicing at several early steps of spliceosome assembly and depends on the activities of both U1 and U2 snRNP proteins to activate splicing...
Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activationA N Kuhn
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, Wisconsin 53706 1532, USA
Genetics 155:1667-82. 2000....
A microbead-based system for identifying and characterizing RNA-protein interactions by flow cytometryAlexander S Brodsky
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Mol Cell Proteomics 1:922-9. 2002..We propose that this strategy, in combination with emerging coded bead systems, can identify RNAs and RNA sequences important for interacting with RNA-binding proteins on genomic scales...
Functional redundancy of worm spliceosomal proteins U1A and U2B''Tassa Saldi
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA
Proc Natl Acad Sci U S A 104:9753-7. 2007..Redundancy results from the fact that one protein can substitute for the other, even though it normally does not...
p54nrb is a component of the snRNP-free U1A (SF-A) complex that promotes pre-mRNA cleavage during polyadenylationSongchun Liang
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School MSB E671, 185 S. Orange Avenue, Newark, NJ 07103, USA
RNA 12:111-21. 2006..We have explored the function of this complex in RNA processing, specifically cleavage and polyadenylation, by performing immunodepletions followed by reconstitution experiments, and have found that p54(nrb) is critical...
The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNAMichael J Law
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90089-9176, USA
Nucleic Acids Res 34:275-85. 2006..Thus, well-positioned positively charged residues can be important for both initial complex formation and complex maintenance, illustrating the multiple roles of electrostatic interactions in protein-RNA complexes...
The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif foldShuying Wang
Department of Structural Biology, Stanford University School of Medicine, California 94305, USA
RNA 12:959-67. 2006....
Interactions of Arabidopsis RS domain containing cyclophilins with SR proteins and U1 and U11 small nuclear ribonucleoprotein-specific proteins suggest their involvement in pre-mRNA SplicingZdravko J Lorkovic
Max F Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Biochemistry, Medical University of Vienna, Dr Bohrgasse 9 3, A 1030 Vienna, Austria
J Biol Chem 279:33890-8. 2004..Alternatively, binding of CypRS64 to proteins important for 5' splice site recognition suggests its involvement in the dynamics of spliceosome assembly...
Anti-U1A monoclonal antibodies recognize unique epitope targets of U1A which are involved in the binding of U1 RNACarol S Lutz
Department of Biochemistry and Molecular Biology, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
J Mol Recognit 15:163-70. 2002..These findings suggest that the structure of the U1A protein may be different when not part of the U1snRNP...
A downstream splicing enhancer is essential for in vitro pre-mRNA splicingB G Yue
Dept of Medical Biochemistry and Microbiology, Uppsala University, Sweden
FEBS Lett 451:10-4. 1999..Also, splice site pairing occurs efficiently in the absence of exonic SR enhancers, emphasizing the significance of a downstream 5' splice site as the enhancer element in vertebrate splicing...
The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factorC S Lutz
Department of Microbiology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA
RNA 4:1493-9. 1998..This suggests that SF-A and/or the SF-A complex(es) perform an important function in both processing reactions and possibly in last exon definition...
U snRNP assembly in yeast involves the La proteinD Xue
Departments of Cell Biology and Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
EMBO J 19:1650-60. 2000..These results suggest that, by stabilizing a 3'-extended form of U4 RNA, Lhp1p facilitates efficient Sm protein binding, thus assisting formation of the U4/U6 snRNP...
An ATP-dependent, Ran-independent mechanism for nuclear import of the U1A and U2B" spliceosome proteinsM Hetzer
European Molecular Biology Laboratory EMBL, D 69117 Heidelberg, Germany
J Cell Biol 148:293-303. 2000..This activity can be solubilized in the presence of elevated MgCl(2). These data suggest that U1A and U2B" import into the nucleus occurs by a hitherto uncharacterized mechanism...
Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in specklesJ Dostie
Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
J Cell Biol 148:239-47. 2000..In addition, overexpression of the dual specificity kinase, Clk/Sty, but not of the catalytically inactive form, results in the dispersion of eIF4E nuclear speckles...
RNA binding specificity of a Drosophila snRNP protein that shares sequence homology with mammalian U1-A and U2-B" proteinsD S Harper
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710
Nucleic Acids Res 20:3645-50. 1992..Furthermore, D25 bound U1 RNA when transfected into mammalian cells. Thus, D25 appears to be a Drosophila homolog of the mammalian U1-A protein, despite its sequence similarity to U2-B"...
Luc7p, a novel yeast U1 snRNP protein with a role in 5' splice site recognitionP Fortes
European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
Genes Dev 13:2425-38. 1999..These data suggest that the loss of Luc7p disrupts U1 snRNP-CBC interaction, and that this interaction contributes to normal 5' splice site recognition...
The SRm160/300 splicing coactivator is required for exon-enhancer functionA G Eldridge
Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5G 1L6, Canada
Proc Natl Acad Sci U S A 96:6125-30. 1999..The results suggest a model for ESE function in which the SRm160/300 splicing coactivator promotes critical interactions between ESE-bound "activators" and the snRNP machinery of the spliceosome...
A comprehensive biochemical and genetic analysis of the yeast U1 snRNP reveals five novel proteinsA Gottschalk
Institut fur Molekularbiologie und Tumorforschung, Philipps Universitat Marburg, Germany
RNA 4:374-93. 1998..Finally, we show that Nam8p/Mud15p contributes to the stability of U1 snRNP...
The yeast splicing factor Mud13p is a commitment complex component and corresponds to CBP20, the small subunit of the nuclear cap-binding complexH V Colot
Howard Hughes Medical Institute, Brandeis University, Department of Biology, Waltham, Massachusetts 02254, USA
Genes Dev 10:1699-708. 1996..Taken together with the accompanying results for a mammalian system, our data indicate that cap-binding proteins as well as the pre-mRNA cap contribute to early steps in spliceosome assembly...
Pre-mRNA processing factors are required for nuclear exportA S Brodsky
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
RNA 6:1737-49. 2000..Taken together, these data graphically display the connections between mRNA processing and nuclear export...
Molecular dynamics simulation of the human U2B" protein complex with U2 snRNA hairpin IV in aqueous solutionJ X Guo
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, 68198-6805 USA
Biophys J 81:630-42. 2001..The stabilizing interaction energy due to bridging water molecules was obtained from ab initio Hartree-Fock and density functional theory calculations...
Modulation of msl-2 5' splice site recognition by Sex-lethalP Förch
Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany
RNA 7:1185-91. 2001..Taken together with previous data, we conclude that efficient retention of msl-2 intron involves inhibition of early recognition of both splice sites by SXL...
NMR studies of U1 snRNA recognition by the N-terminal RNP domain of the human U1A proteinP W Howe
MRC Laboratory of Molecular Biology, Cambridge, UK
EMBO J 13:3873-81. 1994..The quality of the spectra for this complex of 22 kDa demonstrates the feasibility of NMR investigation of RNA-protein complexes...
Research Grants
- Immune Response to Small Nuclear Ribonucleoprotein AutoantigensEric Greidinger; Fiscal Year: 2009..Our research goal is to develop new and effective treatments of these disorders. ..
- APOPTOSIS-MODIFIED SELF ANTIGEN IN RHEUMATIC DISEASEEric Greidinger; Fiscal Year: 2002..In the future, this work may lead to the development of specific immunotherapy strategies for the treatment of Ul-70kDa-associated rheumatic disorders. ..
- Molecular Dynamics of Induced Fit in U1A-RNA ComplexesBETHANY KORMOS; Fiscal Year: 2006..abstract_text> ..
- Immune Response to Small Nuclear Ribonucleoprotein AutoantigensEric L Greidinger; Fiscal Year: 2010..Our research goal is to develop new and effective treatments of these disorders. ..
- Regulation of mRNA Splicing by Mer1pMarc Spingola; Fiscal Year: 2007..This project will elucidate how Mer1p and similar proteins function and will offer important insights towards the basis of diseases like Fragile X Syndrome in humans. ..
- Mechanisms of MeCP2 gene expression regulationCAROL LUTZ; Fiscal Year: 2007..These studies represent an under-explored area of research on MeCP2 gene expression that may have a critical influence in the tissue-specific effects observed in Rett syndrome. ..
- 3' end formation of human type I and II collagen mRNAsCAROL LUTZ; Fiscal Year: 2007....
- Role of G protein Coupling in Fe(ll)-Uptake in BacteriaVinzenz Unger; Fiscal Year: 2006..The fourth aim is to generate crystals of FeoB embedded in a lipid bilayer. Ultimately, this will allow visualization of FeoB, and reveal whether its structure is related to other G protein-coupled membrane proteins. ..
- Spatial changes in gene organization during adipogenesisANTHONY IMBALZANO; Fiscal Year: 2007..Such molecules may represent an entirely new class of targets for future therapies. ..
- Epigenetic Control of AdipogenesisSAID SIF; Fiscal Year: 2010..abstract_text> ..
- TRANSCRIPTION FACTOR FUNCTION IN CHROMATINANTHONY IMBALZANO; Fiscal Year: 2009....
- Structure and Function of Copper TransportersVinzenz Unger; Fiscal Year: 2009..Using the substituted cysteine accessibility method and alanine scanning mutagenesis, we will test this hypothesis by determining how the different transmembrane helices contribute to such a copper uptake. ..
- TRANSCRIPTION FACTOR FUNCTION IN CHROMATINAnthony N Imbalzano; Fiscal Year: 2010....
- TRANSCRIPTION FACTOR FUNCTION IN CHROMATINANTHONY IMBALZANO; Fiscal Year: 2001....
- TRANSCRIPTION FACTOR FUNCTION IN CHROMATINANTHONY IMBALZANO; Fiscal Year: 2005..Aim 3 will probe the generality of the requirement for SWI/SNF enzymes in different differentiation pathways and embryogenesis. ..
- Role of arginine deficiency in pathogenesis of lupusMinoru Satoh; Fiscal Year: 2004..abstract_text> ..
- Tools for Membrane Protein Structure DeterminationVinzenz Unger; Fiscal Year: 2004..This approach may make a large number of membrane proteins amenable to 2D-crystallization and structure determination. ..
- Mechanisms of post-transcriptional regulation of MeCP2CAROL LUTZ; Fiscal Year: 2003..These studies represent under-explored areas of MeCP2 expression that may have a critical influence in the tissue-specific effects observed in Rett syndrome. ..
- PROTEIN ARGININE METHYLATION AND RNA MATURATIONMichael Henry; Fiscal Year: 2003..A better understanding of arginine methylation should not only enhance the understanding of cellular RNA maturation, but also provide insights into viral mechanisms for RNA maturation during cell infection. ..
