Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition

被引：94

作者：

Clery, Antoine ^{[1
]}

Sinha, Rahul ^{[2
]}

Anczukow, Olga ^{[2
]}

Corrionero, Anna ^{[3
,4
]}

Moursy, Ahmed ^{[1
]}

Daubner, Gerrit M. ^{[1
]}

Valcarcel, Juan ^{[3
,4
]}

Krainer, Adrian R. ^{[2
]}

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

机构：

[1] Swiss Fed Inst Technol, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland

[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[3] Univ Pompeu Fabra, Inst Catalana Recerca & Estudis Avancats, Barcelona 08003, Spain

[4] Ctr Regulacio Genom, Barcelona 08003, Spain

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 30期

基金：

美国国家卫生研究院;

关键词：

NMR; protein-RNA complex; splicing factor; NMR STRUCTURE DETERMINATION; MESSENGER-RNA; HNRNP A1; SITE SELECTION; EXON DEFINITION; GENE-EXPRESSION; FACTORS ASF/SF2; FACTOR SF2/ASF; BINDING; APOPTOSIS;

D O I：

10.1073/pnas.1303445110

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：

Serine/arginine (SR) proteins, one of the major families of alternative-splicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one alpha-helix and does not involve the beta-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo-RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound alpha-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.

引用

页码：E2802 / E2811

页数：10

共 80 条

[1] THE ROLE OF SPECIFIC PROTEIN-RNA AND PROTEIN-PROTEIN INTERACTIONS IN POSITIVE AND NEGATIVE CONTROL OF PRE-MESSENGER-RNA SPLICING BY TRANSFORMER-2 [J].