| Structural highlights
Function
PTBP1_HUMAN Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The polypyrimidine tract binding protein (PTB) is an important regulator of alternative splicing that also affects mRNA localization, stabilization, polyadenylation, and translation. NMR structural analysis of the N-terminal half of PTB (residues 55-301) shows a canonical structure for RRM1 but reveals novel extensions to the beta strands and C terminus of RRM2 that significantly modify the beta sheet RNA binding surface. Although PTB contains four RNA recognition motifs (RRMs), it is widely held that only RRMs 3 and 4 are involved in RNA binding and that RRM2 mediates homodimerization. However, we show here not only that the RRMs 1 and 2 contribute substantially to RNA binding but also that full-length PTB is monomeric, with an elongated structure determined by X-ray solution scattering that is consistent with a linear arrangement of the constituent RRMs. These new insights into the structure and RNA binding properties of PTB suggest revised models of its mechanism of action.
Structure and RNA interactions of the N-terminal RRM domains of PTB.,Simpson PJ, Monie TP, Szendroi A, Davydova N, Tyzack JK, Conte MR, Read CM, Cary PD, Svergun DI, Konarev PV, Curry S, Matthews S Structure. 2004 Sep;12(9):1631-43. PMID:15341728[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH. Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science. 2005 Sep 23;309(5743):2054-7. PMID:16179478 doi:http://dx.doi.org/309/5743/2054
- ↑ Simpson PJ, Monie TP, Szendroi A, Davydova N, Tyzack JK, Conte MR, Read CM, Cary PD, Svergun DI, Konarev PV, Curry S, Matthews S. Structure and RNA interactions of the N-terminal RRM domains of PTB. Structure. 2004 Sep;12(9):1631-43. PMID:15341728 doi:10.1016/j.str.2004.07.008
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