An alternative mode of microRNA target recognition

被引：261

作者：

Chi, Sung Wook ^{[1
,3
,4
]}

Hannon, Gregory J. ^{[2
]}

Darnell, Robert B. ^{[1
]}

机构：

[1] Rockefeller Univ, Howard Hughes Med Inst, Lab Neurooncol, New York, NY 10021 USA

[2] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[3] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Grad Sch, Seoul, South Korea

[4] Samsung Med Ctr, Samsung Res Inst Future Med, Seoul, South Korea

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ARGONAUTE SILENCING COMPLEX; MESSENGER-RNAS; CELL-CYCLE; CAENORHABDITIS-ELEGANS; WIDE IDENTIFICATION; BINDING-SITES; PROTEIN; CLIP; BRAIN; TRANSCRIPTS;

D O I：

10.1038/nsmb.2230

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：

MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of similar to 50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise >= 15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.

引用

页码：321 / U80

页数：8

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