iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution

被引：832

作者：

Koenig, Julian ^{[1
]}

Zarnack, Kathi ^{[2
]}

Rot, Gregor ^{[3
]}

Curk, Tomaz ^{[3
]}

Kayikci, Melis ^{[1
]}

Zupan, Blaz ^{[3
]}

Turner, Daniel J. ^{[4
]}

Luscombe, Nicholas M. ^{[2
,5
]}

Ule, Jernej ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

[2] European Bioinformat Inst, European Mol Biol Lab, Cambridge, England

[3] Univ Ljubljana, Fac Comp & Informat Sci, Ljubljana, Slovenia

[4] Wellcome Trust Sanger Inst, Cambridge, England

[5] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 07期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; LASER CROSS-LINKING; RNA-BINDING DOMAIN; PRE-MESSENGER-RNA; C-PROTEINS; GENOME; SITES; BRAIN; CLIP; TRANSCRIPTION;

D O I：

10.1038/nsmb.1838

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：

In the nucleus of eukaryotic cells, nascent transcripts are associated with heterogeneous nuclear ribonucleoprotein (hnRNP) particles that are nucleated by hnRNP C. Despite their abundance, however, it remained unclear whether these particles control pre-mRNA processing. Here, we developed individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to study the role of hnRNP C in splicing regulation. iCLIP data show that hnRNP C recognizes uridine tracts with a defined long-range spacing consistent with hnRNP particle organization. hnRNP particles assemble on both introns and exons but remain generally excluded from splice sites. Integration of transcriptome-wide iCLIP data and alternative splicing profiles into an 'RNA map' indicates how the positioning of hnRNP particles determines their effect on the inclusion of alternative exons. The ability of high-resolution iCLIP data to provide insights into the mechanism of this regulation holds promise for studies of other higher-order ribonucleoprotein complexes.

引用

页码：909 / U166

页数：8

共 34 条

[1] INDEPENDENT DEPOSITION OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS AND SMALL NUCLEAR RIBONUCLEOPROTEIN-PARTICLES AT SITES OF TRANSCRIPTION [J].