3d2s

Structural highlights

Disease

MBNL1_HUMAN Plays a role in the pathogenesis of dystrophia myotonica type 1 (DM1) [MIM:160900. A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. Note=In muscle cells from DM1 patients, MBNL1 is sequestered by DMPK RNAs containing CUG triplet repeat expansions. MBNL1 binding is proportional to repeat length consistent with the direct correlation between the length of repeat expansion and disease severity.

Function

MBNL1_HUMAN Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues.^{[1] [2] [3] [4] [5]}

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, Swanson MS. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 2000 Sep 1;19(17):4439-48. PMID:10970838 doi:10.1093/emboj/19.17.4439
2. ↑ Ho TH, Charlet-B N, Poulos MG, Singh G, Swanson MS, Cooper TA. Muscleblind proteins regulate alternative splicing. EMBO J. 2004 Aug 4;23(15):3103-12. Epub 2004 Jul 15. PMID:15257297 doi:10.1038/sj.emboj.7600300
3. ↑ Paul S, Dansithong W, Kim D, Rossi J, Webster NJ, Comai L, Reddy S. Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing. EMBO J. 2006 Sep 20;25(18):4271-83. Epub 2006 Aug 31. PMID:16946708 doi:10.1038/sj.emboj.7601296
4. ↑ Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S. MBNL1 associates with YB-1 in cytoplasmic stress granules. J Neurosci Res. 2008 Jul;86(9):1994-2002. doi: 10.1002/jnr.21655. PMID:18335541 doi:10.1002/jnr.21655
5. ↑ Warf MB, Diegel JV, von Hippel PH, Berglund JA. The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9203-8. doi:, 10.1073/pnas.0900342106. Epub 2009 May 26. PMID:19470458 doi:10.1073/pnas.0900342106