Structural highlights
Function
[TRA2B_HUMAN] Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA.[1] [2] [3] [4]
Publication Abstract from PubMed
Tra2-beta1 is a unique splicing factor as its single RNA recognition motif (RRM) is located between two RS (arginine-serine) domains. To understand how this protein recognizes its RNA target, we solved the structure of Tra2-beta1 RRM in complex with RNA. The central 5'-AGAA-3' motif is specifically recognized by residues from the beta-sheet of the RRM and by residues from both extremities flanking the RRM. The structure suggests that RNA binding by Tra2-beta1 induces positioning of the two RS domains relative to one another. By testing the effect of Tra2-beta1 and RNA mutations on the splicing of SMN2 exon 7, we validated the importance of the RNA-protein contacts observed in the structure for the function of Tra2-beta1 and determined the functional sequence of Tra2-beta1 in SMN2 exon 7. Finally, we propose a model for the assembly of multiple RNA binding proteins on this exon.
Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-beta1.,Clery A, Jayne S, Benderska N, Dominguez C, Stamm S, Allain FH Nat Struct Mol Biol. 2011 Apr;18(4):443-50. Epub 2011 Mar 13. PMID:21399644[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tacke R, Tohyama M, Ogawa S, Manley JL. Human Tra2 proteins are sequence-specific activators of pre-mRNA splicing. Cell. 1998 Apr 3;93(1):139-48. PMID:9546399
- ↑ Hofmann Y, Wirth B. hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1. Hum Mol Genet. 2002 Aug 15;11(17):2037-49. PMID:12165565
- ↑ Nasim MT, Chernova TK, Chowdhury HM, Yue BG, Eperon IC. HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding. Hum Mol Genet. 2003 Jun 1;12(11):1337-48. PMID:12761049
- ↑ Wang J, Gao QS, Wang Y, Lafyatis R, Stamm S, Andreadis A. Tau exon 10, whose missplicing causes frontotemporal dementia, is regulated by an intricate interplay of cis elements and trans factors. J Neurochem. 2004 Mar;88(5):1078-90. PMID:15009664
- ↑ Clery A, Jayne S, Benderska N, Dominguez C, Stamm S, Allain FH. Molecular basis of purine-rich RNA recognition by the human SR-like protein Tra2-beta1. Nat Struct Mol Biol. 2011 Apr;18(4):443-50. Epub 2011 Mar 13. PMID:21399644 doi:10.1038/nsmb.2001
