U1 snRNA Directly Interacts with Polypyrimidine Tract-Binding Protein during Splicing Repression

被引：78

作者：

Sharma, Shalini ^{[1
]}

Maris, Christophe ^{[3
]}

Allain, Frederic H. -T. ^{[3
]}

Black, Douglas L. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[3] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland

来源：

MOLECULAR CELL | 2011年 / 41卷 / 05期

基金：

美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

NUCLEAR RIBONUCLEOPROTEIN PARTICLE; PRE-MESSENGER-RNA; EXON DEFINITION; NMR-SPECTROSCOPY; PTB; COMPLEX; SPLICEOSOME; SITES; STEM; IDENTIFICATION;

D O I：

10.1016/j.molcel.2011.02.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Splicing of the c-src N1 exon is repressed by the polypyrimidine tract-binding protein (PTB or PTBP1). During exon repression, the U1 snRNP binds properly to the N1 exon 5' splice site but is made inactive by the presence of PTB. Examining the patterns of nuclease protection at this 5' splice site, we find that the interaction of U1 is altered by the adjacent PTB. Interestingly, UV crosslinking identifies a direct contact between the pre-mRNA-bound PTB and the U1 snRNA. EMSA, ITC, and NMR studies show that PTB RRMs 1 and 2 bind the pyrimidine-rich internal loop of U1 snRNA stem loop 4. The PTB/U1 interaction prevents further assembly of the U1 snRNP with spliceosomal components downstream. This precise interaction between a splicing regulator and an snRNA component of the spliceosome points to a range of different mechanisms for splicing regulation.

引用

页码：579 / 588

页数：10

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