Analysis of the RNA-recognition Motif and RS and RGG Domains: Conservation in Metazoan Pre-mRNA Splicing Factors

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1993 Dec 25

PMID 8290338

Citations 297

Authors

E Birney

S Kumar

A R Krainer

Affiliations

Soon will be listed here.

Abstract

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 RNA-recognition 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.

Citing Articles

Myosin-5a facilitates stress granule formation by interacting with G3BP1.

Zhou R, Pan J, Zhang W, Li X Cell Mol Life Sci. 2024; 81(1):430.

PMID: 39387926 PMC: 11467138. DOI: 10.1007/s00018-024-05468-w.

SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.

Phillips J, Park S, Lin C, Cho J, Lim S, Aurora R Br J Cancer. 2024; 131(9):1437-1449.

PMID: 39313574 PMC: 11519869. DOI: 10.1038/s41416-024-02853-x.

Identification of the gene family in rice () and its response to rice blast.

Jiang X, Yu S, Huang Y, Huang J, Liu S, Yang D PeerJ. 2024; 12:e17668.

PMID: 39076776 PMC: 11285362. DOI: 10.7717/peerj.17668.

The glycine-rich domain of GRP7 plays a crucial role in binding long RNAs and facilitating phase separation.

Luhmann K, Seemann S, Martinek N, Ostendorp S, Kehr J Sci Rep. 2024; 14(1):16018.

PMID: 38992080 PMC: 11239674. DOI: 10.1038/s41598-024-66955-5.

SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23.

Segovia D, Adams D, Hoffman N, Safaric Tepes P, Wee T, Cifani P Proc Natl Acad Sci U S A. 2024; 121(21):e2322974121.

PMID: 38743621 PMC: 11126954. DOI: 10.1073/pnas.2322974121.

References

Richter K, Good P, Dawid I . A developmentally regulated, nervous system-specific gene in Xenopus encodes a putative RNA-binding protein. New Biol. 1990; 2(6):556-65. View

Vellard M, Sureau A, Soret J, Martinerie C, Perbal B . A potential splicing factor is encoded by the opposite strand of the trans-spliced c-myb exon. Proc Natl Acad Sci U S A. 1992; 89(7):2511-5. PMC: 48691. DOI: 10.1073/pnas.89.7.2511. View

Mancebo R, Lo P, Mount S . Structure and expression of the Drosophila melanogaster gene for the U1 small nuclear ribonucleoprotein particle 70K protein. Mol Cell Biol. 1990; 10(6):2492-502. PMC: 360606. DOI: 10.1128/mcb.10.6.2492-2502.1990. View

Bossie M, DeHoratius C, BARCELO G, Silver P . A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast. Mol Biol Cell. 1992; 3(8):875-93. PMC: 275646. DOI: 10.1091/mbc.3.8.875. View

Woppmann A, Patschinsky T, Bringmann P, Godt F, Luhrmann R . Characterisation of human and murine snRNP proteins by two-dimensional gel electrophoresis and phosphopeptide analysis of U1-specific 70K protein variants. Nucleic Acids Res. 1990; 18(15):4427-38. PMC: 331261. DOI: 10.1093/nar/18.15.4427. View

Schindelin H, Marahiel M, Heinemann U . Universal nucleic acid-binding domain revealed by crystal structure of the B. subtilis major cold-shock protein. Nature. 1993; 364(6433):164-8. DOI: 10.1038/364164a0. View

Pontius B, Berg P . Renaturation of complementary DNA strands mediated by purified mammalian heterogeneous nuclear ribonucleoprotein A1 protein: implications for a mechanism for rapid molecular assembly. Proc Natl Acad Sci U S A. 1990; 87(21):8403-7. PMC: 54964. DOI: 10.1073/pnas.87.21.8403. View

Saitou N, Nei M . The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4):406-25. DOI: 10.1093/oxfordjournals.molbev.a040454. View

Ge H, Manley J . A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro. Cell. 1990; 62(1):25-34. DOI: 10.1016/0092-8674(90)90236-8. View

10.

Pearson W, Lipman D . Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988; 85(8):2444-8. PMC: 280013. DOI: 10.1073/pnas.85.8.2444. View

11.

Krainer A, Conway G, Kozak D . Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. Genes Dev. 1990; 4(7):1158-71. DOI: 10.1101/gad.4.7.1158. View

12.

Krainer A, Mayeda A, Kozak D, Binns G . Functional expression of cloned human splicing factor SF2: homology to RNA-binding proteins, U1 70K, and Drosophila splicing regulators. Cell. 1991; 66(2):383-94. DOI: 10.1016/0092-8674(91)90627-b. View

13.

Gribskov M, McLachlan A, Eisenberg D . Profile analysis: detection of distantly related proteins. Proc Natl Acad Sci U S A. 1987; 84(13):4355-8. PMC: 305087. DOI: 10.1073/pnas.84.13.4355. View

14.

Mattox W, Ryner L, Baker B . Autoregulation and multifunctionality among trans-acting factors that regulate alternative pre-mRNA processing. J Biol Chem. 1992; 267(27):19023-6. View

15.

Luhrmann R, Kastner B, Bach M . Structure of spliceosomal snRNPs and their role in pre-mRNA splicing. Biochim Biophys Acta. 1990; 1087(3):265-92. DOI: 10.1016/0167-4781(90)90001-i. View

16.

Query C, Bentley R, Keene J . A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell. 1989; 57(1):89-101. DOI: 10.1016/0092-8674(89)90175-x. View

17.

Merrill B, Stone K, Cobianchi F, Wilson S, Williams K . Phenylalanines that are conserved among several RNA-binding proteins form part of a nucleic acid-binding pocket in the A1 heterogeneous nuclear ribonucleoprotein. J Biol Chem. 1988; 263(7):3307-13. View

18.

Lazinski D, Grzadzielska E, Das A . Sequence-specific recognition of RNA hairpins by bacteriophage antiterminators requires a conserved arginine-rich motif. Cell. 1989; 59(1):207-18. DOI: 10.1016/0092-8674(89)90882-9. View

19.

Champlin D, Frasch M, Saumweber H, Lis J . Characterization of a Drosophila protein associated with boundaries of transcriptionally active chromatin. Genes Dev. 1991; 5(9):1611-21. DOI: 10.1101/gad.5.9.1611. View

20.

Kumar A, Casas-Finet J, Luneau C, Karpel R, Merrill B, Williams K . Mammalian heterogeneous nuclear ribonucleoprotein A1. Nucleic acid binding properties of the COOH-terminal domain. J Biol Chem. 1990; 265(28):17094-100. View