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Science 9 April 1993:
Vol. 260. no. 5105, pp. 219 - 222
DOI: 10.1126/science.8385799

Articles

Science, Vol 260, Issue 5105, 219-222
Copyright © 1993 by American Association for the Advancement of Science


articles

Distinct functions of SR proteins in alternative pre-mRNA splicing

AM Zahler, KM Neugebauer, WS Lane, and MB Roth

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

Alternative splicing of precursor messenger RNAs (pre-mRNAs) is a common mechanism of regulating gene expression. SR proteins are a family of pre-mRNA splicing factors that are structurally related and evolutionarily conserved. Any member of the SR family can complement a splicing-deficient extract that lacks the entire family of SR proteins. Here it is demonstrated that particular SR proteins have distinct functions in alternative pre-mRNA splicing in vitro. In addition, SR proteins are differentially expressed in a variety of tissues. These results suggest a fundamental role for SR proteins in the regulation of alternative splicing.


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Regulation of Alternative Splicing of CD45 by Antagonistic Effects of SR Protein Splicing Factors.
G. B. ten Dam, C. F. Zilch, D. Wallace, B. Wieringa, P. C. L. Beverley, L. G. Poels, and G. R. Screaton (2000)
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Identification and Characterization of a Novel Serine-Arginine-Rich Splicing Regulatory Protein.
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C. F. Bourgeois, M. Popielarz, G. Hildwein, and J. Stevenin (1999)
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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)
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The Protein Kinase Clk/Sty Directly Modulates SR Protein Activity: Both Hyper- and Hypophosphorylation Inhibit Splicing.
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Mol. Cell. Biol. 19, 6991-7000
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Transportin-SR, a Nuclear Import Receptor for SR Proteins.
N. Kataoka, J. L. Bachorik, and G. Dreyfuss (1999)
J. Cell Biol. 145, 1145-1152
   Abstract »    Full Text »    PDF »
Variable Levels of Normal RNA in Different Fetal Organs Carrying a Cystic Fibrosis Transmembrane Conductance Regulator Splicing Mutation.
O. CHIBA-FALEK, R. B. PARAD, E. KEREM, and B. KEREM (1999)
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   Abstract »    Full Text »
The SRm160/300 splicing coactivator is required for exon-enhancer function.
A. G. Eldridge, Y. Li, P. A. Sharp, and B. J. Blencowe (1999)
PNAS 96, 6125-6130
   Abstract »    Full Text »    PDF »
atSRp30, one of two SF2/ASF-like proteins from Arabidopsis thaliana, regulates splicing of specific plant genes.
S. Lopato, M. Kalyna, S. Dorner, R. Kobayashi, A. R. Krainer, and A. Barta (1999)
Genes & Dev. 13, 987-1001
   Abstract »    Full Text »
Hepatitis C Virus Core Protein Interacts with Cellular Putative RNA Helicase.
L.-R. You, C.-M. Chen, T.-S. Yeh, T.-Y. Tsai, R.-T. Mai, C.-H. Lin, and Y.-H. W. Lee (1999)
J. Virol. 73, 2841-2853
   Abstract »    Full Text »
Polypyrimidine Tract Binding Protein Functions as a Repressor To Regulate Alternative Splicing of alpha -Actinin Mutally Exclusive Exons.
J. Southby, C. Gooding, and C. W. J. Smith (1999)
Mol. Cell. Biol. 19, 2699-2711
   Abstract »    Full Text »    PDF »
Human step II splicing factor hSlu7 functions in restructuring the spliceosome between the catalytic steps of splicing.
K. Chua and R. Reed (1999)
Genes & Dev. 13, 841-850
   Abstract »    Full Text »
Antagonism between RSF1 and SR proteins for both splice-site recognition in vitro and Drosophila development.
E. Labourier, H.-M. Bourbon, I.-e. Gallouzi, M. Fostier, E. Allemand, and J. Tazi (1999)
Genes & Dev. 13, 740-753
   Abstract »    Full Text »
Substrate Specificities of SR Proteins in Constitutive Splicing Are Determined by Their RNA Recognition Motifs and Composite Pre-mRNA Exonic Elements.
A. Mayeda, G. R. Screaton, S. D. Chandler, X.-D. Fu, and A. R. Krainer (1999)
Mol. Cell. Biol. 19, 1853-1863
   Abstract »    Full Text »    PDF »
Detection of alternative splicing of fibronectin mRNA in a single cell.
T Kumazaki, Y Mitsui, K Hamada, H Sumida, and M Nishiyama (1999)
J. Cell Sci. 112, 1449-1453
   Abstract »    PDF »
Transcriptional Up-regulation of the Delayed Early Gene HRS/SRp40 during Liver Regeneration. INTERACTIONS AMONG YY1, GA-BINDING PROTEINS, AND MITOGENIC SIGNALS.
K. Du, J. I. Leu, Y. Peng, and R. Taub (1998)
J. Biol. Chem. 273, 35208-35215
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The Cellular Localization of the Murine Serine/Arginine-rich Protein Kinase CLK2 Is Regulated by Serine 141 Autophosphorylation.
O. Nayler, F. Schnorrer, S. Stamm, and A. Ullrich (1998)
J. Biol. Chem. 273, 34341-34348
   Abstract »    Full Text »    PDF »
Mutation-Specific Functional Impairments in Distinct Tau Isoforms of Hereditary FTDP-17.
M. Hong, V. Zhukareva, V. Vogelsberg-Ragaglia, Z. Wszolek, L. Reed, B. I. Miller, D. H. Geschwind, T. D. Bird, D. McKeel, A. Goate, et al. (1998)
Science 282, 1914-1917
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Alternative Splicing of the D2 Dopamine Receptor Messenger Ribonucleic Acid Is Modulated by Activated Sex Steroid Receptors in the MMQ Prolactin Cell Line.
D. Guivarc'h, J.-D. Vincent, and P. Vernier (1998)
Endocrinology 139, 4213-4221
   Abstract »    Full Text »    PDF »
The Plant U1 Small Nuclear Ribonucleoprotein Particle 70K Protein Interacts with Two Novel Serine/Arginine –Rich Proteins.
M. Golovkin and A. S. N. Reddy (1998)
PLANT CELL 10, 1637-1648
   Abstract »    Full Text »
Regulation of Alternative Polyadenylation by U1 snRNPs and SRp20.
H. Lou, K. M. Neugebauer, R. F. Gagel, and S. M. Berget (1998)
Mol. Cell. Biol. 18, 4977-4985
   Abstract »    Full Text »
A Serine/Arginine-rich Domain in the Human U1 70k Protein Is Necessary and Sufficient for ASF/SF2 Binding.
W. Cao and M. A. Garcia-Blanco (1998)
J. Biol. Chem. 273, 20629-20635
   Abstract »    Full Text »    PDF »
Characterization of SRp46, a Novel Human SR Splicing Factor Encoded by a PR264/SC35 Retropseudogene.
J. Soret, R. Gattoni, C. Guyon, A. Sureau, M. Popielarz, E. Le Rouzic, S. Dumon, F. Apiou, B. Dutrillaux, H. Voss, et al. (1998)
Mol. Cell. Biol. 18, 4924-4934
   Abstract »    Full Text »
Splicing of Two Internal and Four Carboxyl-terminal Alternative Exons in Nonmuscle Tropomyosin 5 Pre-mRNA Is Independently Regulated during Development.
C. Dufour, R. P. Weinberger, G. Schevzov, P. L. Jeffrey, and P. Gunning (1998)
J. Biol. Chem. 273, 18547-18555
   Abstract »    Full Text »    PDF »
Genetic analysis of the SR protein ASF/SF2: interchangeability of RS domains and negative control of splicing.
J. Wang, S.-H. Xiao, and J. L. Manley (1998)
Genes & Dev. 12, 2222-2233
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Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins.
H.-X. Liu, M. Zhang, and A. R. Krainer (1998)
Genes & Dev. 12, 1998-2012
   Abstract »    Full Text »
SR proteins are sufficient for exon bridging across an intron.
J. M. Stark, D. P. Bazett-Jones, M. Herfort, and M. B. Roth (1998)
PNAS 95, 2163-2168
   Abstract »    Full Text »    PDF »
SRPK2: A Differentially Expressed SR Protein-specific Kinase Involved in Mediating the Interaction and Localization of Pre-mRNA Splicing Factors in Mammalian Cells.
H.-Y. Wang, W. Lin, J. A. Dyck, J. M. Yeakley, Z. Songyang, L. C. Cantley, and X.-D. Fu (1998)
J. Cell Biol. 140, 737-750
   Abstract »    Full Text »    PDF »
Association of Phosphorylated Serine/Arginine (SR) Splicing Factors With The U1-Small Ribonucleoprotein (snRNP) Autoantigen Complex Accompanies Apoptotic Cell Death.
P. J. Utz, M. Hottelet, W. J. van Venrooij, and P. Anderson (1998)
J. Exp. Med. 187, 547-560
   Abstract »    Full Text »    PDF »
Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development.
D. Elliott, K Oghene, G Makarov, O Makarova, T. Hargreave, A. Chandley, I. Eperon, and H. Cooke (1998)
J. Cell Sci. 111, 1255-1265
   Abstract »    PDF »
Regulation of Sex-Specific Selection of fruitless 5' Splice Sites by transformer and transformer-2.
V. Heinrichs, L. C. Ryner, and B. S. Baker (1998)
Mol. Cell. Biol. 18, 450-458
   Abstract »    Full Text »
A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm.
J. F. Cáceres, G. R. Screaton, and A. R. Krainer (1998)
Genes & Dev. 12, 55-66
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Transcription units as RNA processing units.
K. M. Neugebauer and M. B. Roth (1997)
Genes & Dev. 11, 3279-3285
   Full Text »    PDF »
smg mutants affect the expression of alternatively spliced SR protein mRNAs in Caenorhabditis elegans.
M. Morrison, K. S. Harris, and M. B. Roth (1997)
PNAS 94, 9782-9785
   Abstract »    Full Text »    PDF »
Role of the Modular Domains of SR Proteins in Subnuclear Localization and Alternative Splicing Specificity.
J. F. Caceres, T. Misteli, G. R. Screaton, D. L. Spector, and A. R. Krainer (1997)
J. Cell Biol. 138, 225-238
   Abstract »    Full Text »    PDF »
Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription..
K M Neugebauer and M B Roth (1997)
Genes & Dev. 11, 1148-1159
   Abstract »    PDF »
Sequence-specific RNA binding by an SR protein requires RS domain phosphorylation: Creation of an SRp40-specific splicing enhancer.
R. Tacke, Y. Chen, and J. L. Manley (1997)
PNAS 94, 1148-1153
   Abstract »    Full Text »    PDF »
HIV Rev-dependent binding of SF2/ASF to the Rev response element: Possible role in Rev-mediated inhibition of HIV RNA splicing.
D. M. Powell, M. C. Amaral, J. Y. Wu, T. Maniatis, and W. C. Greene (1997)
PNAS 94, 973-978
   Abstract »    Full Text »    PDF »
Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing..
S H Xiao and J L Manley (1997)
Genes & Dev. 11, 334-344
   Abstract »    PDF »
The Mammalian Homolog of Suppressor-of-white-apricot Regulates Alternative mRNA Splicing of CD45 Exon 4and Fibronectin IIICS.
M. Sarkissian, A. Winne, and R. Lafyatis (1996)
J. Biol. Chem. 271, 31106-31114
   Abstract »    Full Text »    PDF »
A protein of the SR family of splicing factors binds extensively to exonic Balbiani ring pre-mRNA and accompanies the RNA from the gene to the nuclear pore..
A T Alzhanova-Ericsson, X Sun, N Visa, E Kiseleva, T Wurtz, and B Daneholt (1996)
Genes & Dev. 10, 2881-2893
   Abstract »    PDF »
Targeted disruption of an essential vertebrate gene: ASF/SF2 is required for cell viability..
J Wang, Y Takagaki, and J L Manley (1996)
Genes & Dev. 10, 2588-2599
   Abstract »    PDF »
SRPK1 and Clk/Sty Protein Kinases Show Distinct Substrate Specificities for Serine/Arginine-rich Splicing Factors.
K. Colwill, L. L. Feng, J. M. Yeakley, G. D. Gish, J. F. Caceres, T. Pawson, and X.-D. Fu (1996)
J. Biol. Chem. 271, 24569-24575
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Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer..
K W Lynch and T Maniatis (1996)
Genes & Dev. 10, 2089-2101
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SR proteins and splicing control..
J L Manley and R Tacke (1996)
Genes & Dev. 10, 1569-1579
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An intron enhancer recognized by splicing factors activates polyadenylation..
H Lou, R F Gagel, and S M Berget (1996)
Genes & Dev. 10, 208-219
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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
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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
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The Gene Encoding Human Splicing Factor 9G8.
M. Popielarz, Y. Cavaloc, M.-G. Mattei, R. Gattoni, and J. Stvenin (1995)
J. Biol. Chem. 270, 17830-17835
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A Mammalian Activity Required for the Second Step of Pre-messenger RNA Splicing.
L. A. Lindsey, A. J. Crow, and M. A. Garcia-Blanco (1995)
J. Biol. Chem. 270, 13415-13421
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Multiple Splicing Signals Control Alternative Intron Retention of Bovine Growth Hormone Pre-mRNA.
W. P. Dirksen, Q. Sun, and F. M. Rottman (1995)
J. Biol. Chem. 270, 5346-5352
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Soma-specific expression and cloning of PSI, a negative regulator of P element pre-mRNA splicing..
C W Siebel, A Admon, and D C Rio (1995)
Genes & Dev. 9, 269-283
   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 »
Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
J. Caceres, S Stamm, D. Helfman, and A. Krainer (1994)
Science 265, 1706-1709
   Abstract »    PDF »
Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element..
G S Huh and R O Hynes (1994)
Genes & Dev. 8, 1561-1574
   Abstract »    PDF »
Alternative pre-mRNA splicing: factors involved in splice site selection.
P. Norton (1994)
J. Cell Sci. 107, 1-7
   PDF »
A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding..
A Lavigueur, H La Branche, A R Kornblihtt, and B Chabot (1993)
Genes & Dev. 7, 2405-2417
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