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.

Science 24 December 1993:
Vol. 262. no. 5142, pp. 2035 - 2039
DOI: 10.1126/science.8266100
Prev | Table of Contents | Next

Articles

Science, Vol 262, Issue 5142, 2035-2039
Copyright © 1993 by American Association for the Advancement of Science

articles

Involvement of U6 snRNA in 5' splice site selection

S Kandels-Lewis and B Seraphin

European Molecular Biology, Laboratory, Heidelberg, Germany.

Two models describing the interaction between U6 small nuclear RNA (snRNA) and the 5' splice site of introns have been proposed on the basis of cross-linking experiments. Here it is shown that a conserved sequence present in U6 snRNA forms base pairs with conserved nucleotides at the 5' splice junction and that this interaction is involved in 5' splice site choice. These results demonstrate a specific function for U6 snRNA in splicing and suggest that U6 snRNA has a proofreading role during splice site selection. A model is presented in which this new interaction, in concert with previously described interactions between U6 snRNA, U2 snRNA, and the pre-messenger RNA, would position the branch point near the 5' splice site for the catalysis of the first splicing step.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Protein-free small nuclear RNAs catalyze a two-step splicing reaction.
S. Valadkhan, A. Mohammadi, Y. Jaladat, and S. Geisler (2009)
PNAS 106, 11901-11906
   Abstract »    Full Text »    PDF »
U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing.
K. Fukumura, I. Taniguchi, H. Sakamoto, M. Ohno, and K. Inoue (2009)
Nucleic Acids Res. 37, 1907-1914
   Abstract »    Full Text »    PDF »
Identification and characterization of a short 2'-3' bond-forming ribozyme.
D. J. Smith and M. M. Konarska (2009)
RNA 15, 8-13
   Abstract »    Full Text »    PDF »
A DNA damage signal activates and derepresses exon inclusion in Drosophila TAF1 alternative splicing.
M. S. Marengo and D. A. Wassarman (2008)
RNA 14, 1681-1695
   Abstract »    Full Text »    PDF »
The U1, U2 and U5 snRNAs crosslink to the 5' exon during yeast pre-mRNA splicing.
J. C. McGrail and R. T. O'Keefe (2008)
Nucleic Acids Res. 36, 814-825
   Abstract »    Full Text »    PDF »
Three essential and conserved regions of the group II intron are proximal to the 5'-splice site.
A. de Lencastre and A. M. Pyle (2008)
RNA 14, 11-24
   Abstract »    Full Text »    PDF »
Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics.
X. Roca, A. J. Olson, A. R. Rao, E. Enerly, V. N. Kristensen, A.-L. Borresen-Dale, B. S. Andresen, A. R. Krainer, and R. Sachidanandam (2008)
Genome Res. 18, 77-87
   Abstract »    Full Text »    PDF »
Protein-free spliceosomal snRNAs catalyze a reaction that resembles the first step of splicing.
S. Valadkhan, A. Mohammadi, C. Wachtel, and J. L. Manley (2007)
RNA 13, 2300-2311
   Abstract »    Full Text »    PDF »
In vitro and in silico analysis reveals an efficient algorithm to predict the splicing consequences of mutations at the 5' splice sites.
K. Sahashi, A. Masuda, T. Matsuura, J. Shinmi, Z. Zhang, Y. Takeshima, M. Matsuo, G. Sobue, and K. Ohno (2007)
Nucleic Acids Res. 35, 5995-6003
   Abstract »    Full Text »    PDF »
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.
E. Buratti, M. Chivers, J. Kralovicova, M. Romano, M. Baralle, A. R. Krainer, and I. Vorechovsky (2007)
Nucleic Acids Res. 35, 4250-4263
   Abstract »    Full Text »    PDF »
A Sequence Motif in the Simian Virus 40 (SV40) Early Core Promoter Affects Alternative Splicing of Transcribed mRNA.
E. Gendra, D. F. Colgan, B. Meany, and M. M. Konarska (2007)
J. Biol. Chem. 282, 11648-11657
   Abstract »    Full Text »    PDF »
A subset of Mer1p-dependent introns requires Bud13p for splicing activation and nuclear retention.
F. W. Scherrer Jr and M. Spingola (2006)
RNA 12, 1361-1372
   Abstract »    Full Text »    PDF »
A simple principle to explain the evolution of pre-mRNA splicing..
J.-M. Izquierdo and J. Valcarcel (2006)
Genes & Dev. 20, 1679-1684
   Full Text »    PDF »
Dissection of Prp8 protein defines multiple interactions with crucial RNA sequences in the catalytic core of the spliceosome.
I. A. TURNER, C. M. NORMAN, M. J. CHURCHER, and A. J. NEWMAN (2006)
RNA 12, 375-386
   Abstract »    Full Text »    PDF »
Characterization of hCINAP, a Novel Coilin-interacting Protein Encoded by a Transcript from the Transcription Factor TAFIID32 Locus.
N. Santama, S. C. Ogg, A. Malekkou, S. E. Zographos, K. Weis, and A. I. Lamond (2005)
J. Biol. Chem. 280, 36429-36441
   Abstract »    Full Text »    PDF »
Proximity of the U12 snRNA with both the 5' Splice Site and the Branch Point during Early Stages of Spliceosome Assembly.
M. J. Frilander and X. Meng (2005)
Mol. Cell. Biol. 25, 4813-4825
   Abstract »    Full Text »    PDF »
Determinants of the inherent strength of human 5' splice sites.
X. ROCA, R. SACHIDANANDAM, and A. R. KRAINER (2005)
RNA 11, 683-698
   Abstract »    Full Text »    PDF »
Multiple functions for the invariant AGC triad of U6 snRNA.
A. K. HILLIKER and J. P. STALEY (2004)
RNA 10, 921-928
   Abstract »    Full Text »    PDF »
Mer1p is a modular splicing factor whose function depends on the conserved U2 snRNP protein Snu17p.
M. Spingola, J. Armisen, and M. Ares Jr (2004)
Nucleic Acids Res. 32, 1242-1250
   Abstract »    Full Text »    PDF »
Intrinsic differences between authentic and cryptic 5' splice sites.
X. Roca, R. Sachidanandam, and A. R. Krainer (2003)
Nucleic Acids Res. 31, 6321-6333
   Abstract »    Full Text »    PDF »
Mutagenesis Suggests Several Roles of Snu114p in Pre-mRNA Splicing.
C. Bartels, H. Urlaub, R. Luhrmann, and P. Fabrizio (2003)
J. Biol. Chem. 278, 28324-28334
   Abstract »    Full Text »    PDF »
Spatial Organization of Protein-RNA Interactions in the Branch Site-3' Splice Site Region during pre-mRNA Splicing in Yeast.
D. S. McPheeters and P. Muhlenkamp (2003)
Mol. Cell. Biol. 23, 4174-4186
   Abstract »    Full Text »    PDF »
The U1 snRNP Base Pairs with the 5' Splice Site within a Penta-snRNP Complex.
H. Malca, N. Shomron, and G. Ast (2003)
Mol. Cell. Biol. 23, 3442-3455
   Abstract »    Full Text »    PDF »
Saccharomyces cerevisiae Bzz1p Is Implicated with Type I Myosins in Actin Patch Polarization and Is Able To Recruit Actin-Polymerizing Machinery In Vitro.
A. Soulard, T. Lechler, V. Spiridonov, A. Shevchenko, A. Shevchenko, R. Li, and B. Winsor (2002)
Mol. Cell. Biol. 22, 7889-7906
   Abstract »    Full Text »    PDF »
A Novel Yeast U2 snRNP Protein, Snu17p, Is Required for the First Catalytic Step of Splicing and for Progression of Spliceosome Assembly.
A. Gottschalk, C. Bartels, G. Neubauer, R. Lührmann, and P. Fabrizio (2001)
Mol. Cell. Biol. 21, 3037-3046
   Abstract »    Full Text »
Novel Point Mutation in the Splice Donor Site of Exon-Intron Junction 6 of the Androgen Receptor Gene in a Patient with Partial Androgen Insensitivity Syndrome.
I. Sammarco, P. Grimaldi, P. Rossi, M. Cappa, C. Moretti, G. Frajese, and R. Geremia (2000)
J. Clin. Endocrinol. Metab. 85, 3256-3261
   Abstract »    Full Text »
Suppressors of a Cold-Sensitive Mutation in Yeast U4 RNA Define Five Domains in the Splicing Factor Prp8 That Influence Spliceosome Activation.
A. N. Kuhn and D. A. Brow (2000)
Genetics 155, 1667-1682
   Abstract »    Full Text »
The Allele-Specific Suppressor sup-39 Alters Use of Cryptic Splice Sites in Caenorhabditis elegans.
A. B. Roller, D. C. Hoffman, and A. M. Zahler (2000)
Genetics 154, 1169-1179
   Abstract »    Full Text »
Role of adenine functional groups in the recognition of the 3'-splice-site AG during the second step of pre-mRNA splicing.
R. K. Gaur, L. Beigelman, P. Haeberli, and T. Maniatis (2000)
PNAS 97, 115-120
   Abstract »    Full Text »    PDF »
The Saccharomyces cerevisiae Homologue of Human Wiskott-Aldrich Syndrome Protein Las17p Interacts with the Arp2/3 Complex.
A. Madania, P. Dumoulin, S. Grava, H. Kitamoto, C. Schärer-Brodbeck, A. Soulard, V. Moreau, and B. Winsor (1999)
Mol. Biol. Cell 10, 3521-3538
   Abstract »    Full Text »
Allele-specific genetic interactions between Prp8 and RNA active site residues suggest a function for Prp8 at the catalytic core of the spliceosome.
C. A. Collins and C. Guthrie (1999)
Genes & Dev. 13, 1970-1982
   Abstract »    Full Text »
Functional interactions of Prp8 with both splice sites at the spliceosomal catalytic center.
M. Siatecka, J. L. Reyes, and M. M. Konarska (1999)
Genes & Dev. 13, 1983-1993
   Abstract »    Full Text »
Saccharomyces cerevisiae Putative G Protein, Gtr1p, Which Forms Complexes With Itself and a Novel Protein Designated as Gtr2p, Negatively Regulates the Ran/Gsp1p G Protein Cycle Through Gtr2p.
N. Nakashima, E. Noguchi, and T. Nishimoto (1999)
Genetics 152, 853-867
   Abstract »    Full Text »
A Novel Genetic Screen for snRNP Assembly Factors in Yeast Identifies a Conserved Protein, Sad1p, Also Required for Pre-mRNA Splicing.
Z. Lygerou, G. Christophides, and B. Seraphin (1999)
Mol. Cell. Biol. 19, 2008-2020
   Abstract »    Full Text »    PDF »
Pseudouridine Mapping in the Saccharomyces cerevisiae Spliceosomal U Small Nuclear RNAs (snRNAs) Reveals that Pseudouridine Synthase Pus1p Exhibits a Dual Substrate Specificity for U2 snRNA and tRNA.
S. Massenet, Y. Motorin, D. L. J. Lafontaine, E. C. Hurt, H. Grosjean, and C. Branlant (1999)
Mol. Cell. Biol. 19, 2142-2154
   Abstract »    Full Text »    PDF »
Detection of a Novel ATP-Dependent Cross-Linked Protein at the 5' Splice Site-U1 Small Nuclear RNA Duplex by Methylene Blue-Mediated Photo-Cross-Linking.
Z.-R. Liu, B. Sargueil, and C. W. J. Smith (1998)
Mol. Cell. Biol. 18, 6910-6920
   Abstract »    Full Text »
The Pre-mRNA 5' Cap Determines Whether U6 Small Nuclear RNA Succeeds U1 Small Nuclear Ribonucleoprotein Particle at 5' Splice Sites.
L. O'Mullane and I. C. Eperon (1998)
Mol. Cell. Biol. 18, 7510-7520
   Abstract »    Full Text »
The Human U5-220kD Protein (hPrp8) Forms a Stable RNA-Free Complex with Several U5-Specific Proteins, Including an RNA Unwindase, a Homologue of Ribosomal Elongation Factor EF-2, and a Novel WD-40 Protein.
T. Achsel, K. Ahrens, H. Brahms, S. Teigelkamp, and R. Lührmann (1998)
Mol. Cell. Biol. 18, 6756-6766
   Abstract »    Full Text »
Interactions within the Yeast Sm Core Complex: from Proteins to Amino Acids.
A. Camasses, E. Bragado-Nilsson, R. Martin, B. Séraphin, and R. Bordonné (1998)
Mol. Cell. Biol. 18, 1956-1966
   Abstract »    Full Text »
Synthetic Lethality of Yeast slt Mutations with U2 Small Nuclear RNA Mutations Suggests Functional Interactions between U2 and U5 snRNPs That Are Important for Both Steps of Pre-mRNA Splicing.
D. Xu, D. J. Field, S.-J. Tang, A. Moris, B. P. Bobechko, and J. D. Friesen (1998)
Mol. Cell. Biol. 18, 2055-2066
   Abstract »    Full Text »
Site-specific crosslinking of mammalian U11 and U6atac to the 5' splice site of an AT-AC intron.
Y.-T. Yu and J. A. Steitz (1997)
PNAS 94, 6030-6035
   Abstract »    Full Text »    PDF »
Sequence Divergence Associated with Species-specific Splicing of the Nonmuscle beta-Tropomyosin Alternative Exon.
A.-M. Pret and M. Y. Fiszman (1996)
J. Biol. Chem. 271, 11511-11517
   Abstract »    Full Text »    PDF »
U1 snRNA promotes the selection of nearby 5' splice sites by U6 snRNA in mammalian cells..
D Y Hwang and J B Cohen (1996)
Genes & Dev. 10, 338-350
   Abstract »    PDF »
A U6 snRNA:pre-mRNA interaction can be rate-limiting for U1-independent splicing..
J D Crispino and P A Sharp (1995)
Genes & Dev. 9, 2314-2323
   Abstract »    PDF »
In Vitro Splicing Deficiency Induced by a C to T Mutation at Position -3 in the Intron 10 Acceptor Site of the Phenylalanine Hydroxylase Gene in a Patient with Phenylketonuria.
J. Jaruzelska, V. Abadie, Y. d'Aubenton-Carafa, E. Brody, A. Munnich, and J.ël. Marie (1995)
J. Biol. Chem. 270, 20370-20375
   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 »
A novel U2-U6 snRNA structure is necessary for mammalian mRNA splicing..
J S Sun and J L Manley (1995)
Genes & Dev. 9, 843-854
   Abstract »    PDF »
SR proteins can compensate for the loss of U1 snRNP functions in vitro..
W Y Tarn and J A Steitz (1994)
Genes & Dev. 8, 2704-2717
   Abstract »    PDF »
Complementation by SR proteins of pre-mRNA splicing reactions depleted of U1 snRNP.
J. Crispino, B. Blencowe, and P. Sharp (1994)
Science 265, 1866-1869
   Abstract »    PDF »
U4/U5/U6 snRNP recognizes the 5' splice site in the absence of U2 snRNP..
B B Konforti and M M Konarska (1994)
Genes & Dev. 8, 1962-1973
   Abstract »    PDF »
The prespliceosome components SAP 49 and SAP 145 interact in a complex implicated in tethering U2 snRNP to the branch site..
P Champion-Arnaud and R Reed (1994)
Genes & Dev. 8, 1974-1983
   Abstract »    PDF »
A group III intron is formed from domains of two individual group II introns..
L Hong and R B Hallick (1994)
Genes & Dev. 8, 1589-1599
   Abstract »    PDF »
A tertiary interaction in the Tetrahymena intron contributes to selection of the 5' splice site..
W D Downs and T R Cech (1994)
Genes & Dev. 8, 1198-1211
   Abstract »    PDF »
Randomization-selection analysis of snRNAs in vivo: evidence for a tertiary interaction in the spliceosome..
H D Madhani and C Guthrie (1994)
Genes & Dev. 8, 1071-1086
   Abstract »    PDF »
Guides to the heart of the spliceosome.
J. Wise (1993)
Science 262, 1978-1979
   PDF »
The U5 and U6 small nuclear RNAs as active site components of the spliceosome.
E. Sontheimer and J. Steitz (1993)
Science 262, 1989-1996
   Abstract »    PDF »


To Advertise     Find Products

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