RNA looping by PTB: Evidence using FRET and NMR spectroscopy for a role in splicing repression

被引：85

作者：

Lamichhane, Rajan ^{[2
]}

Daubner, Gerrit M. ^{[1
]}

Thomas-Crusells, Judith ^{[1
]}

Auweter, Sigrid D. ^{[1
]}

Manatschal, Cristina ^{[1
]}

Austin, Keyunna S. ^{[2
]}

Valniuk, Oksana ^{[2
]}

Allain, Frederic H. -T. ^{[1
]}

Rueda, David ^{[2
]}

机构：

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

[2] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 09期

基金：

美国国家科学基金会; 美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

alternative splicing; polypyrimidine tract-binding protein; protein-RNA interactions; TRACT-BINDING-PROTEIN; EXON DEFINITION; ENERGY-TRANSFER; COMPLEX; EXPRESSION; INCLUSION; MOLECULE; DOMAIN; MOTIF; TIME;

D O I：

10.1073/pnas.0907072107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Alternative splicing plays an important role in generating proteome diversity. The polypyrimidine tract-binding protein (PTB) is a key alternative splicing factor involved in exon repression. It has been proposed that PTB acts by looping out exons flanked by pyrimidine tracts. We present fluorescence, NMR, and in vivo splicing data in support of a role of PTB in inducing RNA loops. We show that the RNA recognition motifs (RRMs) 3 and 4 of PTB can bind two distant pyrimidine tracts and bring their 5' and 3' ends in close proximity, thus looping the RNA. Efficient looping requires an intervening sequence of 15 nucleotides or longer between the pyrimidine tracts. RRM3 and RRM4 bind the 5' and the 3' pyrimidine tracts, respectively, in a specific directionality and work synergistically for efficient splicing repression in vivo.

引用

页码：4105 / 4110

页数：6

共 35 条

[31] Structure of the two most C-terminal RNA recognition motifs of PTB using segmental isotope labeling [J].