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Nucleic Acids Research, 1993, Vol. 21, No. 25 5803-5816
© 1993


SURVEY AND SUMMARY

Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors

Ewan Birney+, Sanjay Kumar§ and Adrian R. Krainer*

Cold Spring Harbor Laboratory, PO Box 100, 1 Bungtown Road, Cold Spring Harbor NY 11724-2208, USA

To whom correspondence should be addressed

Received July 30, 1993. Revised October 27, 1993. Accepted October 27, 1993.

We present a systematic analysis of sequence motifs found in metazoan protein factors involved in constitutive pre-mRNA splicing and in alternative splicing regulation. Using profile analysis we constructed a database enriched in protein sequences containing one or more presumptive copies of the RNArecognition motif (RRM). We provide an accurate alignment of RRMs and structure-based criteria for identifying new RRMs, including many that lack the prototype RNP-1 submotif. We present a comprehensive table of 125 sequences containing 252 RRMs, including 22 previously unreported RRMs in 17 proteins. The presence of a putative RRM in these proteins, which are implicated in a variety of cellular processes, strongly suggests that their function involves binding to RNA. Unreported homologies in the RRM-enriched database to the metazoan SR family of splicing factors are described for an Arg-rich human nuclear protein and two yeast proteins (S. pombe mei2 and S. cerevisiae Npl3). We have rigorously tested the phylogenetic relationships of a large sample of RRMs. This analysis indicates that the RRM is an ancient conserved region (ACR) that has diversified by duplication of genes and intragenic domains. Statistical analyses and classification of repeated Arg-Ser (RS)and RGG domains in various protein splicing factors are presented.


+Balliol College, Oxford, OX1 3BJ, UK

§New England Biolabs, Beverly, MA 01915, USA


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Evidence for Splice Site Pairing via Intron Definition in Schizosaccharomyces pombe
Mol. Cell. Biol., November 1, 2000; 20(21): 7955 - 7970.
[Abstract] [Full Text]


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JCBHome page
C. Y. Yun and X.-D. Fu
Conserved Sr Protein Kinase Functions in Nuclear Import and Its Action Is Counteracted by Arginine Methylation in Saccharomyces cerevisiae
J. Cell Biol., August 21, 2000; 150(4): 707 - 718.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
A. Eversole and N. Maizels
In Vitro Properties of the Conserved Mammalian Protein hnRNP D Suggest a Role in Telomere Maintenance
Mol. Cell. Biol., August 1, 2000; 20(15): 5425 - 5432.
[Abstract] [Full Text]


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Nucleic Acids ResHome page
C. Crosio, P. P. Boyl, F. Loreni, P. Pierandrei-Amaldi, and F. Amaldi
La protein has a positive effect on the translation of TOP mRNAs in vivo
Nucleic Acids Res., August 1, 2000; 28(15): 2927 - 2934.
[Abstract] [Full Text] [PDF]


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GeneticsHome page
M. J. Lisbin, M. Gordon, Y. M. Yannoni, and K. White
Function of RRM Domains of Drosophila melanogaster ELAV: RNP1 Mutations and RRM Domain Replacements With ELAV Family Proteins and SXL
Genetics, August 1, 2000; 155(4): 1789 - 1798.
[Abstract] [Full Text]


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JCBHome page
P. Lasko
The Drosophila melanogaster Genome: Translation Factors and RNA Binding Proteins
J. Cell Biol., July 24, 2000; 150(2): 51 - 56.
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Genes Dev.Home page
X. Chen, A. M. Quinn, and S. L. Wolin
Ro ribonucleoproteins contribute to the resistance of Deinococcus radiodurans to ultraviolet irradiation
Genes & Dev., April 1, 2000; 14(7): 777 - 782.
[Abstract] [Full Text]


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Hum Mol GenetHome page
J.P. Venables, D.J. Elliott, O.V. Makarova, E.M. Makarov, H.J. Cooke, and I.C. Eperon
RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2{beta} and affect splicing
Hum. Mol. Genet., March 22, 2000; 9(5): 685 - 694.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
J. Zhou, K. Hidaka, and B. Futcher
The Est1 Subunit of Yeast Telomerase Binds the Tlc1 Telomerase RNA
Mol. Cell. Biol., March 15, 2000; 20(6): 1947 - 1955.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
M.-C. Lai, R.-I. Lin, S.-Y. Huang, C.-W. Tsai, and W.-Y. Tarn
A Human Importin-beta Family Protein, Transportin-SR2, Interacts with the Phosphorylated RS Domain of SR Proteins
J. Biol. Chem., March 10, 2000; 275(11): 7950 - 7957.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
A. E. McBride, V. H. Weiss, H. K. Kim, J. M. Hogle, and P. A. Silver
Analysis of the Yeast Arginine Methyltransferase Hmt1p/Rmt1p and Its in Vivo Function. COFACTOR BINDING AND SUBSTRATE INTERACTIONS
J. Biol. Chem., February 4, 2000; 275(5): 3128 - 3136.
[Abstract] [Full Text] [PDF]


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DevelopmentHome page
C Pazman, C. Mayes, M Fanto, S. Haynes, and M Mlodzik
Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling
Development, January 4, 2000; 127(8): 1715 - 1725.
[Abstract] [PDF]


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Genes Dev.Home page
R. Perriman and M. Ares Jr.
ATP can be dispensable for prespliceosome formation in yeast
Genes & Dev., January 1, 2000; 14(1): 97 - 107.
[Abstract] [Full Text]


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Proc. Natl. Acad. Sci. USAHome page
E. Welin Henriksson, M. Wahren-Herlenius, I. Lundberg, E. Mellquist, and I. Pettersson
Key residues revealed in a major conformational epitope of the U1-70K protein
PNAS, December 7, 1999; 96(25): 14487 - 14492.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. Gordon, T. K. Sengupta, C. A. Phillips, S. M. O'Malley, K. R. Williams, and E. K. Spicer
Identification of the RNA Binding Domain of T4 RegA Protein by Structure-based Mutagenesis
J. Biol. Chem., November 5, 1999; 274(45): 32265 - 32273.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
S. G. Sobel and S. L. Wolin
Two Yeast La Motif-containing Proteins Are RNA-binding Proteins that Associate with Polyribosomes
Mol. Biol. Cell, November 1, 1999; 10(11): 3849 - 3862.
[Abstract] [Full Text]


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GeneticsHome page
A. G. Davies, C. A. Spike, J. E. Shaw, and R. K. Herman
Functional Overlap Between the mec-8 Gene and Five sym Genes in Caenorhabditis elegans
Genetics, September 1, 1999; 153(1): 117 - 134.
[Abstract] [Full Text]


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J. Virol.Home page
M. Piron, T. Delaunay, J. Grosclaude, and D. Poncet
Identification of the RNA-Binding, Dimerization, and eIF4GI-Binding Domains of Rotavirus Nonstructural Protein NSP3
J. Virol., July 1, 1999; 73(7): 5411 - 5421.
[Abstract] [Full Text]


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Mol. Biol. CellHome page
K. Boudonck, L. Dolan, and P. J. Shaw
The Movement of Coiled Bodies Visualized in Living Plant Cells by the Green Fluorescent Protein
Mol. Biol. Cell, July 1, 1999; 10(7): 2297 - 2307.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
L. A. Hanakahi, H. Sun, and N. Maizels
High Affinity Interactions of Nucleolin with G-G-paired rDNA
J. Biol. Chem., May 28, 1999; 274(22): 15908 - 15912.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
C. W. Siebel, L. Feng, C. Guthrie, and X.-D. Fu
Conservation in budding yeast of a kinase specific for SR splicing factors
PNAS, May 11, 1999; 96(10): 5440 - 5445.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
J. Ding, M. K. Hayashi, Y. Zhang, L. Manche, A. R. Krainer, and R.-M. Xu
Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA
Genes & Dev., May 1, 1999; 13(9): 1102 - 1115.
[Abstract] [Full Text]


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Proc. Natl. Acad. Sci. USAHome page
S. M. Crowder, R. Kanaar, D. C. Rio, and T. Alber
Absence of interdomain contacts in the crystal structure of the RNA recognition motifs of Sex-lethal
PNAS, April 27, 1999; 96(9): 4892 - 4897.
[Abstract] [Full Text] [PDF]


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Genes Dev.Home page
S. Lopato, M. Kalyna, S. Dorner, R. Kobayashi, A. R. Krainer, and A. Barta
atSRp30, one of two SF2/ASF-like proteins from Arabidopsis thaliana, regulates splicing of specific plant genes
Genes & Dev., April 15, 1999; 13(8): 987 - 1001.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
L. Perrin, P. Romby, P. Laurenti, H. Berenger, S. Kallenbach, H.-M. Bourbon, and J. Pradel
The Drosophila Modifier of Variegation modulo Gene Product Binds Specific RNA Sequences at the Nucleolus and Interacts with DNA and Chromatin in a Phosphorylation-dependent Manner
J. Biol. Chem., March 5, 1999; 274(10): 6315 - 6323.
[Abstract] [Full Text] [PDF]


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Mol. Cell. Biol.Home page
A. Mayeda, G. R. Screaton, S. D. Chandler, X.-D. Fu, and A. R. Krainer
Substrate Specificities of SR Proteins in Constitutive Splicing Are Determined by Their RNA Recognition Motifs and Composite Pre-mRNA Exonic Elements
Mol. Cell. Biol., March 1, 1999; 19(3): 1853 - 1863.
[Abstract] [Full Text] [PDF]


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J. Cell Sci.Home page
F Weighardt, F Cobianchi, L Cartegni, I Chiodi, A Villa, S Riva, and G Biamonti
A novel hnRNP protein (HAP/SAF-B) enters a subset of hnRNP complexes and relocates in nuclear granules in response to heat shock
J. Cell Sci., January 5, 1999; 112(10): 1465 - 1476.
[Abstract] [PDF]



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