Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins

被引：390

作者：

Wang, Eric T. ^{[1
,2
,3
]}

Cody, Neal A. L. ^{[5
]}

Jog, Sonali ^{[6
]}

Biancolella, Michela ^{[6
]}

Wang, Thomas T. ^{[1
,3
]}

Treacy, Daniel J. ^{[1
]}

Luo, Shujun ^{[7
]}

Schroth, Gary P. ^{[7
]}

Housman, David E. ^{[1
,2
,3
]}

Reddy, Sita ^{[6
]}

Lecuyer, Eric ^{[5
,8
]}

Burge, Christopher B. ^{[1
,2
,3
,4
]}

机构：

[1] MIT, Dept Biol, Cambridge, MA 02142 USA

[2] MIT, Div Hlth Sci & Technol, Cambridge, MA 02142 USA

[3] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA

[4] MIT, Dept Biol Engn, Cambridge, MA 02142 USA

[5] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada

[6] Univ So Calif, Los Angeles, CA 90033 USA

[7] Illumina Inc, Hayward, CA 94545 USA

[8] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

来源：

CELL | 2012年 / 150卷 / 04期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

MYOTONIC-DYSTROPHY; ENDOPLASMIC-RETICULUM; GENE-EXPRESSION; STEM-CELLS; SYNAPSE FORMATION; MBNL1; TRANSLATION; DROSOPHILA; REVEALS; BINDING;

D O I：

10.1016/j.cell.2012.06.041

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：

The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 30 splice site or near the downstream 50 splice site, respectively. Transcriptomic analysis of subcellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs in both mouse and Drosophila cells, and Mbnl-dependent translation and protein secretion were observed for a subset of mRNAs with Mbnl-dependent localization. These findings hold several new implications for DM pathogenesis.

引用

页码：710 / 724

页数：15

共 65 条

[1] RNA-dependent integrin α3 protein localization regulated by the Muscleblind-like protein MLP1 [J].