| Structural highlights
Function
[KHDR3_HUMAN] RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. May play a role as a negative regulator of cell growth. Inhibits cell proliferation. Involved in splice site selection of vascular endothelial growth factor. Induces an increased concentration-dependent incorporation of exon in CD44 pre-mRNA by direct binding to purine-rich exonic enhancer. RNA-binding abilities are down-regulated by tyrosine kinase PTK6. Involved in post-transcriptional regulation of HIV-1 gene expression. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro.[1] [2] [3]
Publication Abstract from PubMed
Sam68 and T-STAR are members of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins. T-STAR is a tissue-specific paralogue that regulates the alternative splicing of neuronal pre-mRNAs. STAR proteins differ from most splicing factors, in that they contain a single RNA-binding domain. Their specificity of RNA recognition is thought to arise from their property to homodimerize, but how dimerization influences their function remains unknown. Here, we establish at atomic resolution how T-STAR and Sam68 bind to RNA, revealing an unexpected mode of dimerization different from other members of the STAR family. We further demonstrate that this unique dimerization interface is crucial for their biological activity in splicing regulation, and suggest that the increased RNA affinity through dimer formation is a crucial parameter enabling these proteins to select their functional targets within the transcriptome.
Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68.,Feracci M, Foot JN, Grellscheid SN, Danilenko M, Stehle R, Gonchar O, Kang HS, Dalgliesh C, Meyer NH, Liu Y, Lahat A, Sattler M, Eperon IC, Elliott DJ, Dominguez C Nat Commun. 2016 Jan 13;7:10355. doi: 10.1038/ncomms10355. PMID:26758068[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee J, Burr JG. Salpalpha and Salpbeta, growth-arresting homologs of Sam68. Gene. 1999 Nov 15;240(1):133-47. PMID:10564820
- ↑ Reddy TR, Suhasini M, Xu W, Yeh LY, Yang JP, Wu J, Artzt K, Wong-Staal F. A role for KH domain proteins (Sam68-like mammalian proteins and quaking proteins) in the post-transcriptional regulation of HIV replication. J Biol Chem. 2002 Feb 22;277(8):5778-84. Epub 2001 Dec 7. PMID:11741900 doi:http://dx.doi.org/10.1074/jbc.M106836200
- ↑ Cohen CD, Doran PP, Blattner SM, Merkle M, Wang GQ, Schmid H, Mathieson PW, Saleem MA, Henger A, Rastaldi MP, Kretzler M. Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor. J Am Soc Nephrol. 2005 Jul;16(7):1958-65. Epub 2005 May 18. PMID:15901763 doi:http://dx.doi.org/10.1681/ASN.2005020204
- ↑ Feracci M, Foot JN, Grellscheid SN, Danilenko M, Stehle R, Gonchar O, Kang HS, Dalgliesh C, Meyer NH, Liu Y, Lahat A, Sattler M, Eperon IC, Elliott DJ, Dominguez C. Structural basis of RNA recognition and dimerization by the STAR proteins T-STAR and Sam68. Nat Commun. 2016 Jan 13;7:10355. doi: 10.1038/ncomms10355. PMID:26758068 doi:http://dx.doi.org/10.1038/ncomms10355
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