Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 28 March 1986:
Vol. 231. no. 4745, pp. 1534 - 1539
DOI: 10.1126/science.3952495
Prev | Table of Contents | Next

Articles

Science, Vol 231, Issue 4745, 1534-1539
Copyright © 1986 by American Association for the Advancement of Science

articles

Heterogeneous nuclear ribonucleoproteins: role in RNA splicing

YD Choi, PJ Grabowski, PA Sharp, and G Dreyfuss

Splicing in vitro of a messenger RNA (mRNA) precursor (pre-mRNA) is inhibited by a monoclonal antibody to the C proteins (anti-C) of the heterogeneous nuclear RNA (hnRNA)-ribonucleoprotein (hnRNP) particles. This antibody, 4F4, inhibits an early step of the reaction: cleavage at the 3' end of the upstream exon and the formation of the intron lariat. In contrast, boiled 4F4, or a different monoclonal antibody (designated 2B12) to the C proteins, or antibodies to other hnRNP proteins (120 and 68 kilodaltons) and nonimmune mouse antibodies have no inhibitory effect. The 4F4 antibody does not prevent the adenosine triphosphate-dependent formation of a 60S splicing complex (spliceosome). Furthermore, the 60S splicing complex contains C proteins, and it can be immunoprecipitated with 4F4. Depletion of C proteins from the splicing extract by immunoadsorption with either of the two monoclonal antibodies to the C proteins (4F4 or 2B12) results in the loss of splicing activity, whereas mock-depletion with nonimmune mouse antibodies bodies has no effect. A 60S splicing complex does not form in a C protein-depleted nuclear extract. These results indicate an essential role for proteins of the hnRNP complex in the splicing of mRNA precursors.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Multiple and Specific mRNA Processing Targets for the Major Human hnRNP Proteins.
J. P. Venables, C.-S. Koh, U. Froehlich, E. Lapointe, S. Couture, L. Inkel, A. Bramard, E. R. Paquet, V. Watier, M. Durand, et al. (2008)
Mol. Cell. Biol. 28, 6033-6043
   Abstract »    Full Text »    PDF »
Functional Characterization of Heterogeneous Nuclear Ribonuclear Protein C1/C2 in Vitamin D Resistance: A NOVEL RESPONSE ELEMENT-BINDING PROTEIN.
H. Chen, M. Hewison, and J. S. Adams (2006)
J. Biol. Chem. 281, 39114-39120
   Abstract »    Full Text »    PDF »
Immunoprecipitation of spliceosomal RNAs by antisera to galectin-1 and galectin-3.
W. Wang, J. W. Park, J. L. Wang, and R. J. Patterson (2006)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Identification of Proteins Cleaved Downstream of Caspase Activation in Monocytes Undergoing Macrophage Differentiation.
S. Cathelin, C. Rebe, L. Haddaoui, N. Simioni, F. Verdier, M. Fontenay, S. Launay, P. Mayeux, and E. Solary (2006)
J. Biol. Chem. 281, 17779-17788
   Abstract »    Full Text »    PDF »
Derepression of the Her-2 uORF is mediated by a novel post-transcriptional control mechanism in cancer cells.
A. Mehta, C. R. Trotta, and S. W. Peltz (2006)
Genes & Dev. 20, 939-953
   Abstract »    Full Text »    PDF »
Regulation of expression by promoters versus internal ribosome entry site in the 5'-untranslated sequence of the human cyclin-dependent kinase inhibitor p27kip1.
Z. Liu, Z. Dong, B. Han, Y. Yang, Y. Liu, and J.-T. Zhang (2005)
Nucleic Acids Res. 33, 3763-3771
   Abstract »    Full Text »    PDF »
Heterogenous Nuclear Ribonucleoprotein F Modulates Angiotensinogen Gene Expression in Rat Kidney Proximal Tubular Cells.
C.-C. Wei, D.-F. Guo, S.-L. Zhang, J. R. Ingelfinger, and J. S.D. Chan (2005)
J. Am. Soc. Nephrol. 16, 616-628
   Abstract »    Full Text »    PDF »
Nuclear efflux of heterogeneous nuclear ribonucleoprotein C1/C2 in apoptotic cells: a novel nuclear export dependent on Rho-associated kinase activation.
H.-H. Lee, C.-L. Chien, H.-K. Liao, Y.-J. Chen, and Z.-F. Chang (2004)
J. Cell Sci. 117, 5579-5589
   Abstract »    Full Text »    PDF »
SUMO Modification of Heterogeneous Nuclear Ribonucleoproteins.
M. T. Vassileva and M. J. Matunis (2004)
Mol. Cell. Biol. 24, 3623-3632
   Abstract »    Full Text »    PDF »
Demonstrating internal ribosome entry sites in eukaryotic mRNAs using stringent RNA test procedures.
M. E. VAN EDEN, M. P. BYRD, K. W. SHERRILL, and R. E. LLOYD (2004)
RNA 10, 720-730
   Abstract »    Full Text »    PDF »
Cloning and Characterization of Glycine-Rich RNA-Binding Protein cDNAs in the Moss Physcomitrella patens.
T. Nomata, Y. Kabeya, and N. Sato (2004)
Plant Cell Physiol. 45, 48-56
   Abstract »    Full Text »    PDF »
The Internal Ribosome Entry Site-Mediated Translation of Antiapoptotic Protein XIAP Is Modulated by the Heterogeneous Nuclear Ribonucleoproteins C1 and C2.
M. Holcik, B. W. Gordon, and R. G. Korneluk (2003)
Mol. Cell. Biol. 23, 280-288
   Abstract »    Full Text »
Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics.
A. Tefferi, E. D. Wieben, G. W. Dewald, D. A. H. Whiteman, M. E. Bernard, and T. C. Spelsberg (2002)
Mayo Clin. Proc. 77, 785-808
   Abstract »    PDF »
Heterogeneous Nuclear Ribonucleoproteins C1 and C2 Associate with the RNA Component of Human Telomerase.
L. P. Ford, J. M. Suh, W. E. Wright, and J. W. Shay (2000)
Mol. Cell. Biol. 20, 9084-9091
   Abstract »    Full Text »
Human Genomic Sequences That Inhibit Splicing.
W. G. Fairbrother and L. A. Chasin (2000)
Mol. Cell. Biol. 20, 6816-6825
   Abstract »    Full Text »
hnRNP C Is Required for Postimplantation Mouse Development but Is Dispensable for Cell Viability.
D. J. Williamson, S. Banik-Maiti, J. DeGregori, and H. E. Ruley (2000)
Mol. Cell. Biol. 20, 4094-4105
   Abstract »    Full Text »
The Levels of the bancal Product, a Drosophila Homologue of Vertebrate hnRNP K Protein, Affect Cell Proliferation and Apoptosis in Imaginal Disc Cells.
B. Charroux, C. Angelats, L. Fasano, S. Kerridge, and C. Vola (1999)
Mol. Cell. Biol. 19, 7846-7856
   Abstract »    Full Text »    PDF »
hnRNP H Is a Component of a Splicing Enhancer Complex That Activates a c-src Alternative Exon in Neuronal Cells.
M.-Y. Chou, N. Rooke, C. W. Turck, and D. L. Black (1999)
Mol. Cell. Biol. 19, 69-77
   Abstract »    Full Text »    PDF »
The hrp23 Protein in the Balbiani Ring Pre-mRNP Particles Is Released Just before or at the Binding of the Particles to the Nuclear Pore Complex.
X. Sun, A. T. Alzhanova-Ericsson, N. Visa, Y. Aissouni, J. Zhao, and B. Daneholt (1998)
J. Cell Biol. 142, 1181-1193
   Abstract »    Full Text »    PDF »
Vav Binding to Heterogeneous Nuclear Ribonucleoprotein (hnRNP) C. EVIDENCE FOR Vav-hnRNP INTERACTIONS IN AN RNA-DEPENDENT MANNER.
F. Romero, A. Germani, E. Puvion, J. Camonis, N. Varin-Blank, S. Gisselbrecht, and S. Fischer (1998)
J. Biol. Chem. 273, 5923-5931
   Abstract »    Full Text »    PDF »
Modulation of AUUUA Response Element Binding by Heterogeneous Nuclear Ribonucleoprotein A1 in Human T Lymphocytes. THE ROLES OF CYTOPLASMIC LOCATION, TRANSCRIPTION, AND PHOSPHORYLATION.
B. J. Hamilton, C. M. Burns, R. C. Nichols, and W. F. C. Rigby (1997)
J. Biol. Chem. 272, 28732-28741
   Abstract »    Full Text »    PDF »
Transportin-mediated Nuclear Import of Heterogeneous Nuclear RNP Proteins.
M. C. Siomi, P. S. Eder, N. Kataoka, L. Wan, Q. Liu, and G. Dreyfuss (1997)
J. Cell Biol. 138, 1181-1192
   Abstract »    Full Text »    PDF »
Cloning of Human 2H9 Heterogeneous Nuclear Ribonucleoproteins. RELATION WITH SPLICING AND EARLY HEAT SHOCK-INDUCED SPLICING ARREST.
D. Mahe, P. Mahl, R. Gattoni, N. Fischer, M.-G. Mattei, J. Stevenin, and J.-P. Fuchs (1997)
J. Biol. Chem. 272, 1827-1836
   Abstract »    Full Text »    PDF »
Heteronuclear Ribonucleoproteins C1 and C2, Components of the Spliceosome, Are Specific Targets of Interleukin 1beta -converting Enzyme-like Proteases in Apoptosis.
N. Waterhouse, S. Kumar, Q. Song, P. Strike, L. Sparrow, G. Dreyfuss, E. S. Alnemri, G. Litwack, M. Lavin, and D. Watters (1996)
J. Biol. Chem. 271, 29335-29341
   Abstract »    Full Text »    PDF »
The C-group Heterogeneous Nuclear Ribonucleoprotein Proteins Bind to the 5' Stem-Loop of the U2 Small Nuclear Ribonucleoprotein Particle.
J. Temsamani and T. Pederson (1996)
J. Biol. Chem. 271, 24922-24926
   Abstract »    Full Text »    PDF »
trans-Activation by the hnRNP K Protein Involves an Increase in RNA Synthesis from the Reporter Genes.
M.-H. Lee, S. Mori, and P. Raychaudhuri (1996)
J. Biol. Chem. 271, 3420-3427
   Abstract »    Full Text »    PDF »
The generally expressed hnRNP F is involved in a neural-specific pre-mRNA splicing event..
H Min, R C Chan, and D L Black (1995)
Genes & Dev. 9, 2659-2671
   Abstract »    PDF »
The UUAG-specific RNA Binding Protein, Heterogeneous Nuclear Ribonucleoprotein D0.
Y. Kajita, J.-i. Nakayama, M. Aizawa, and F. Ishikawa (1995)
J. Biol. Chem. 270, 22167-22175
   Abstract »    Full Text »    PDF »
Nucleolin and Heterogeneous Nuclear Ribonucleoprotein C Proteins Specifically Interact with the 3`-Untranslated Region of Amyloid Protein Precursor mRNA.
S. H. E. Zaidi and J. S. Malter (1995)
J. Biol. Chem. 270, 17292-17298
   Abstract »    Full Text »    PDF »
Disruption of Base-paired U4[IMAGE]U6 Small Nuclear RNAs Induced by Mammalian Heterogeneous Nuclear Ribonucleoprotein C Protein.
T. Forné, F. Rossi, E. Labourier, E. Antoine, G. Cathala, C. Brunel, and J. Tazi (1995)
J. Biol. Chem. 270, 16476-16481
   Abstract »    Full Text »    PDF »
Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA..
J M Romac and J D Keene (1995)
Genes & Dev. 9, 1400-1410
   Abstract »    PDF »
Regulation of tissue-specific P-element pre-mRNA splicing requires the RNA-binding protein PSI..
C W Siebel, R Kanaar, and D C Rio (1994)
Genes & Dev. 8, 1713-1725
   Abstract »    PDF »
Cloning and characterization of PSF, a novel pre-mRNA splicing factor..
J G Patton, E B Porro, J Galceran, P Tempst, and B Nadal-Ginard (1993)
Genes & Dev. 7, 393-406
   Abstract »    PDF »
Interaction of the human autoantigen p150 with splicing snRNPs.
B. Blencowe, M Carmo-Fonseca, S. Behrens, R Luhrmann, and A. Lamond (1993)
J. Cell Sci. 105, 685-697
   Abstract »    PDF »
U1 snRNP targets an essential splicing factor, U2AF65, to the 3' splice site by a network of interactions spanning the exon..
B E Hoffman and P J Grabowski (1992)
Genes & Dev. 6, 2554-2568
   Abstract »    PDF »
An essential splicing factor, SLU7, mediates 3' splice site choice in yeast..
D Frank and C Guthrie (1992)
Genes & Dev. 6, 2112-2124
   Abstract »    PDF »
The mechanism of somatic inhibition of Drosophila P-element pre-mRNA splicing: multiprotein complexes at an exon pseudo-5' splice site control U1 snRNP binding..
C W Siebel, L D Fresco, and D C Rio (1992)
Genes & Dev. 6, 1386-1401
   Abstract »    PDF »
Characterization of cDNAs encoding the polypyrimidine tract-binding protein..
A Gil, P A Sharp, S F Jamison, and M A Garcia-Blanco (1991)
Genes & Dev. 5, 1224-1236
   Abstract »    PDF »
Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing..
J G Patton, S A Mayer, P Tempst, and B Nadal-Ginard (1991)
Genes & Dev. 5, 1237-1251
   Abstract »    PDF »
Control of alternative splicing by the differential binding of U1 small nuclear ribonucleoprotein particle.
H. Kuo, F. Nasim, and P. Grabowski (1991)
Science 251, 1045-1050
   Abstract »    PDF »
Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells..
A R Krainer, G C Conway, and D Kozak (1990)
Genes & Dev. 4, 1158-1171
   Abstract »    PDF »
A Sequential splicing mechanism promotes selection of an optimal exon by repositioning a downstream 5' splice site in preprotachykinin pre-mRNA..
F H Nasim, P A Spears, H M Hoffmann, H C Kuo, and P J Grabowski (1990)
Genes & Dev. 4, 1172-1184
   Abstract »    PDF »
Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma..
W Mattox, M J Palmer, and B S Baker (1990)
Genes & Dev. 4, 789-805
   Abstract »    PDF »
Identification and purification of a 62,000-dalton protein that binds specifically to the polypyrimidine tract of introns..
M A Garcia-Blanco, S F Jamison, and P A Sharp (1989)
Genes & Dev. 3, 1874-1886
   Abstract »    PDF »
RNA-binding proteins as developmental regulators..
R J Bandziulis, M S Swanson, and G Dreyfuss (1989)
Genes & Dev. 3, 431-437
   PDF »
RNA Splicing and Genes.
P. A. Sharp (1988)
JAMA 260, 3035-3041
   Abstract »    PDF »
Correct in vivo splicing of the mouse immunoglobulin kappa light-chain pre-mRNA is dependent on 5' splice-site position even in the absence of transcription..
D H Kedes and J A Steitz (1988)
Genes & Dev. 2, 1448-1459
   Abstract »    PDF »
Virus-specific splicing inhibitor in extracts from cells infected with HIV-1.
D Gutman and C. Goldenberg (1988)
Science 241, 1492-1495
   Abstract »    PDF »
Presplicing complex formation requires two proteins and U2 snRNP..
A Kramer (1988)
Genes & Dev. 2, 1155-1167
   Abstract »    PDF »
Splice site selection, rate of splicing, and alternative splicing on nascent transcripts..
A L Beyer and Y N Osheim (1988)
Genes & Dev. 2, 754-765
   Abstract »    PDF »
Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins..
S Pinol-Roma, Y D Choi, M J Matunis, and G Dreyfuss (1988)
Genes & Dev. 2, 215-227
   Abstract »    PDF »
Electrophoretic separation of polyadenylation-specific complexes..
H Skolnik-David, C L Moore, and P A Sharp (1987)
Genes & Dev. 1, 672-682
   Abstract »    PDF »
A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation..
J R Couto, J Tamm, R Parker, and C Guthrie (1987)
Genes & Dev. 1, 445-455
   Abstract »    PDF »
Splicing of yeast nuclear pre-mRNA in vitro requires a functional 40S spliceosome and several extrinsic factors..
R J Lin, A J Lustig, and J Abelson (1987)
Genes & Dev. 1, 7-18
   Abstract »    PDF »
Splicing of messenger RNA precursors.
P. Sharp (1987)
Science 235, 766-771
   Abstract »    PDF »
Splicing of Messenger RNA Precursors.
P.A. Sharp, M.M. Konarksa, P.J. Grabowski, A.I. Lamond, R. Marciniak, and S.R. Seiler (1987)
Cold Spring Harb Symp Quant Biol 52, 277-285
   Abstract »    PDF »
The Splicing Factor U1C Represses EWS/FLI-mediated Transactivation.
L. L. Knoop and S. J. Baker (2000)
J. Biol. Chem. 275, 24865-24871
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)