2dnq

Structural highlights

Function

RBM4_HUMAN RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Lai MC, Kuo HW, Chang WC, Tarn WY. A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 2003 Mar 17;22(6):1359-69. PMID:12628928 doi:http://dx.doi.org/10.1093/emboj/cdg126
2. ↑ Lin JC, Tarn WY. Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB. Mol Cell Biol. 2005 Nov;25(22):10111-21. PMID:16260624 doi:http://dx.doi.org/10.1128/MCB.25.22.10111-10121.2005
3. ↑ Kar A, Havlioglu N, Tarn WY, Wu JY. RBM4 interacts with an intronic element and stimulates tau exon 10 inclusion. J Biol Chem. 2006 Aug 25;281(34):24479-88. PMID:16777844 doi:10.1074/jbc.M603971200
4. ↑ Markus MA, Heinrich B, Raitskin O, Adams DJ, Mangs H, Goy C, Ladomery M, Sperling R, Stamm S, Morris BJ. WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo. Exp Cell Res. 2006 Oct 15;312(17):3379-88. PMID:16934801 doi:10.1016/j.yexcr.2006.07.008
5. ↑ Lin JC, Hsu M, Tarn WY. Cell stress modulates the function of splicing regulatory protein RBM4 in translation control. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2235-40. PMID:17284590 doi:10.1073/pnas.0611015104
6. ↑ Hock J, Weinmann L, Ender C, Rudel S, Kremmer E, Raabe M, Urlaub H, Meister G. Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Rep. 2007 Nov;8(11):1052-60. Epub 2007 Oct 12. PMID:17932509 doi:http://dx.doi.org/7401088
7. ↑ Lin JC, Tarn WY. RNA-binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation. J Biol Chem. 2009 Dec 11;284(50):34658-65. PMID:19801630 doi:10.1074/jbc.M109.032946
8. ↑ Kar A, Fushimi K, Zhou X, Ray P, Shi C, Chen X, Liu Z, Chen S, Wu JY. RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site. Mol Cell Biol. 2011 May;31(9):1812-21. doi: 10.1128/MCB.01149-10. Epub 2011 Feb, 22. PMID:21343338 doi:http://dx.doi.org/10.1128/MCB.01149-10
9. ↑ Lin JC, Tarn WY. RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing. J Cell Biol. 2011 May 2;193(3):509-20. doi: 10.1083/jcb.201007131. Epub 2011 Apr , 25. PMID:21518792 doi:http://dx.doi.org/10.1083/jcb.201007131
10. ↑ Yang Y, Lee GC, Nakagaki-Silva E, Huang Y, Peacey M, Partridge R, Gooding C, Smith CWJ. Cell-type specific regulator RBPMS switches alternative splicing via higher-order oligomerization and heterotypic interactions with other splicing regulators. Nucleic Acids Res. 2023 Oct 13;51(18):9961-9982. PMID:37548402 doi:10.1093/nar/gkad652