WW Domain-mediated Interactions Reveal a Spliceosome-associated Protein That Binds a Third Class of Proline-rich Motif: the Proline Glycine and Methionine-rich Motif

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1998 Sep 2

PMID 9724750

Citations 55

Authors

M T Bedford

R REED

P Leder

Affiliations

Soon will be listed here.

Abstract

Pre-mRNA splicing requires the bridging of the 5' and 3' ends of the intron. In yeast, this bridging involves interactions between the WW domains in the splicing factor PRP40 and a proline-rich domain in the branchpoint binding protein, BBP. Using a proline-rich domain derived from formin (a product of the murine limb deformity locus), we have identified a family of murine formin binding proteins (FBP's), each of which contains one or more of a special class of tyrosine-rich WW domains. Two of these WW domains, in the proteins FBP11 and FBP21, are strikingly similar to those found in the yeast splicing factor PRP40. We show that FBP21 is present in highly purified spliceosomal complex A, is associated with U2 snRNPs, and colocalizes with splicing factors in nuclear speckle domains. Moreover, FBP21 interacts directly with the U1 snRNP protein U1C, the core snRNP proteins SmB and SmB', and the branchpoint binding protein SF1/mBBP. Thus, FBP21 may play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex.

Citing Articles

Exploration of phosphoproteomic association during epimorphic regeneration.

Banu S, Anusha P, Mandal K, Idris M Sci Rep. 2025; 15(1):4854.

PMID: 39924536 PMC: 11808059. DOI: 10.1038/s41598-024-84735-z.

Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.

Engal E, Oja K, Maroofian R, Geminder O, Le T, Marzin P Am J Hum Genet. 2023; 110(12):2112-2119.

PMID: 37963460 PMC: 10716347. DOI: 10.1016/j.ajhg.2023.10.013.

Pre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal.

Glasser E, Maji D, Biancon G, Keedakkatt Puthenpeedikakkal A, Cavender C, Tebaldi T Nucleic Acids Res. 2022; 50(9):5299-5312.

PMID: 35524551 PMC: 9128377. DOI: 10.1093/nar/gkac287.

Heterozygous loss of WBP11 function causes multiple congenital defects in humans and mice.

Martin E, Enriquez A, Sparrow D, Humphreys D, McInerney-Leo A, Leo P Hum Mol Genet. 2020; 29(22):3662-3678.

PMID: 33276377 PMC: 7823106. DOI: 10.1093/hmg/ddaa258.

E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease.

Zhang Y, Qian H, Wu B, You S, Wu S, Lu S Int J Biol Sci. 2020; 16(14):2727-2740.

PMID: 33110392 PMC: 7586430. DOI: 10.7150/ijbs.48437.

References

Kaelin Jr W, Krek W, Sellers W, DeCaprio J, Ajchenbaum F, Fuchs C . Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992; 70(2):351-64. DOI: 10.1016/0092-8674(92)90108-o. View

Chan D, Bedford M, Leder P . Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains. EMBO J. 1996; 15(5):1045-54. PMC: 450002. View

Behrens S, Tyc K, Kastner B, Reichelt J, Luhrmann R . Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. Mol Cell Biol. 1993; 13(1):307-19. PMC: 358910. DOI: 10.1128/mcb.13.1.307-319.1993. View

Spector D . Nuclear organization of pre-mRNA processing. Curr Opin Cell Biol. 1993; 5(3):442-7. DOI: 10.1016/0955-0674(93)90009-f. View

Brosi R, Groning K, Behrens S, Luhrmann R, Kramer A . Interaction of mammalian splicing factor SF3a with U2 snRNP and relation of its 60-kD subunit to yeast PRP9. Science. 1993; 262(5130):102-5. DOI: 10.1126/science.8211112. View

Bennett M, REED R . Correspondence between a mammalian spliceosome component and an essential yeast splicing factor. Science. 1993; 262(5130):105-8. DOI: 10.1126/science.8211113. View

Staknis D, REED R . Direct interactions between pre-mRNA and six U2 small nuclear ribonucleoproteins during spliceosome assembly. Mol Cell Biol. 1994; 14(5):2994-3005. PMC: 358667. DOI: 10.1128/mcb.14.5.2994-3005.1994. View

Musacchio A, Wilmanns M, Saraste M . Structure and function of the SH3 domain. Prog Biophys Mol Biol. 1994; 61(3):283-97. DOI: 10.1016/0079-6107(94)90003-5. View

Andre B, Springael J . WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65. Biochem Biophys Res Commun. 1994; 205(2):1201-5. DOI: 10.1006/bbrc.1994.2793. View

10.

Hofmann K, Bucher P . The rsp5-domain is shared by proteins of diverse functions. FEBS Lett. 1995; 358(2):153-7. DOI: 10.1016/0014-5793(94)01415-w. View

11.

Bork P, Sudol M . The WW domain: a signalling site in dystrophin?. Trends Biochem Sci. 1994; 19(12):531-3. DOI: 10.1016/0968-0004(94)90053-1. View

12.

Billings P, Allen R, JENSEN F, Hoch S . Anti-RNP monoclonal antibodies derived from a mouse strain with lupus-like autoimmunity. J Immunol. 1982; 128(3):1176-80. View

13.

Billings P, Barton J, Hoch S . A murine monoclonal antibody recognizes the 13,000 molecular weight polypeptide of the Sm small nuclear ribonucleoprotein complex. J Immunol. 1985; 135(1):428-32. View

14.

Woychik R, Stewart T, Davis L, DEustachio P, Leder P . An inherited limb deformity created by insertional mutagenesis in a transgenic mouse. Nature. 1985; 318(6041):36-40. DOI: 10.1038/318036a0. View

15.

Sharpe N, Williams D, Norton P, Latchman D . Expression of the SmB' splicing protein in rodent cells capable of following an alternative RNA splicing pathway. FEBS Lett. 1989; 243(2):132-6. DOI: 10.1016/0014-5793(89)80114-0. View

16.

Rokeach L, Jannatipour M, Haselby J, Hoch S . Primary structure of a human small nuclear ribonucleoprotein polypeptide as deduced by cDNA analysis. J Biol Chem. 1989; 264(9):5024-30. View

17.

Habets W, Hoet M, de Jong B, van der Kemp A, van Venrooij W . Mapping of B cell epitopes on small nuclear ribonucleoproteins that react with human autoantibodies as well as with experimentally-induced mouse monoclonal antibodies. J Immunol. 1989; 143(8):2560-6. View

18.

Macias M, Hyvonen M, Baraldi E, Schultz J, Sudol M, Saraste M . Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide. Nature. 1996; 382(6592):646-9. DOI: 10.1038/382646a0. View

19.

Arning S, Gruter P, Bilbe G, Kramer A . Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996; 2(8):794-810. PMC: 1369416. View

20.

Einbond A, Sudol M . Towards prediction of cognate complexes between the WW domain and proline-rich ligands. FEBS Lett. 1996; 384(1):1-8. DOI: 10.1016/0014-5793(96)00263-3. View