Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges

被引：259

作者：

Lovci, Michael T. ^{[1
,2
,3
]}

Ghanem, Dana ^{[4
]}

Marr, Henry ^{[4
]}

Arnold, Justin ^{[1
,2
,3
]}

Gee, Sherry ^{[4
]}

Parra, Marilyn ^{[4
]}

Liang, Tiffany Y. ^{[1
,2
,3
]}

Stark, Thomas J. ^{[1
,2
,3
]}

Gehman, Lauren T. ^{[5
,6
]}

Hoon, Shawn ^{[7
,8
]}

Massirer, Katlin B. ^{[1
,2
,3
]}

Pratt, Gabriel A. ^{[1
,2
,3
]}

Black, Douglas L. ^{[5
,6
]}

Gray, Joe W. ^{[9
]}

Conboy, John G. ^{[4
]}

Yeo, Gene W. ^{[1
,2
,3
,7
,10
]}

机构：

[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Stem Cell Program, San Diego, CA 92103 USA

[3] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[4] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USA

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

[6] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA

[7] Agcy Sci Technol & Res, Inst Biomed Sci, Mol Engn Lab, Singapore, Singapore

[8] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore

[9] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97201 USA

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2013年 / 20卷 / 12期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ANALYSIS; SECONDARY STRUCTURE; SACCHAROMYCES-CEREVISIAE; EXON INCLUSION; ELEMENTS; CODE; REVEALS; NETWORK; TDP-43; AUTISM;

D O I：

10.1038/nsmb.2699

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：

Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins.

引用

页码：1434 / 1442

页数：9

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