Predicting effective microRNA target sites in mammalian mRNAs

被引:5579
作者
Agarwal, Vikram [1 ,2 ,3 ]
Bell, George W. [4 ]
Nam, Jin-Wu [1 ,2 ,5 ]
Bartel, David P. [1 ,2 ]
机构
[1] Howard Hughes Med Inst, Whitehead Inst Biomed Res, Cambridge, MA 02138 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA
[4] Whitehead Inst Biomed Res, Bioinformat & Res Comp, Cambridge, MA USA
[5] Hanyang Univ, Coll Nat Sci, Dept Life Sci, Seoul 133791, South Korea
来源
ELIFE | 2015年 / 4卷
基金
美国国家科学基金会;
关键词
GENOME BROWSER DATABASE; BINDING-SITES; ALTERNATIVE POLYADENYLATION; WIDE IDENTIFICATION; IN-VIVO; MIRNA; WIDESPREAD; REPRESSION; PROTEIN; GENES;
D O I
10.7554/eLife.05005
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV-crosslinking approaches suggest that many mRNAs are targeted through non-canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks.
引用
收藏
页数:38
相关论文
共 123 条
[91]   Functional microRNA targets in protein coding sequences [J].
Reczko, Martin ;
Maragkakis, Manolis ;
Alexiou, Panagiotis ;
Grosse, Ivo ;
Hatzigeorgiou, Artemis G. .
BIOINFORMATICS, 2012, 28 (06) :771-776
[92]   The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J].
Reinhart, BJ ;
Slack, FJ ;
Basson, M ;
Pasquinelli, AE ;
Bettinger, JC ;
Rougvie, AE ;
Horvitz, HR ;
Ruvkun, G .
NATURE, 2000, 403 (6772) :901-906
[93]   Human microRNAs target a functionally distinct population of genes with AT-rich 3′ UTRs [J].
Robins, H ;
Press, WH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15557-15562
[94]   Incorporating structure to predict microRNA targets [J].
Robins, H ;
Li, Y ;
Padgett, RW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (11) :4006-4009
[95]   edgeR: a Bioconductor package for differential expression analysis of digital gene expression data [J].
Robinson, Mark D. ;
McCarthy, Davis J. ;
Smyth, Gordon K. .
BIOINFORMATICS, 2010, 26 (01) :139-140
[96]   Requirement of bic/microRNA-155 for normal immune function [J].
Rodriguez, Antony ;
Vigorito, Elena ;
Clare, Simon ;
Warren, Madhuri V. ;
Couttet, Philippe ;
Soond, Dalya R. ;
van Dongen, Stijn ;
Grocock, Russell J. ;
Das, Partha P. ;
Miska, Eric A. ;
Vetrie, David ;
Okkenhaug, Klaus ;
Enright, Anton J. ;
Dougan, Gordon ;
Turner, Martin ;
Bradley, Allan .
SCIENCE, 2007, 316 (5824) :608-611
[97]  
Saito Takaya, 2012, Silence, V3, P3, DOI 10.1186/1758-907X-3-3
[98]   Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites [J].
Sandberg, Rickard ;
Neilson, Joel R. ;
Sarma, Arup ;
Sharp, Phillip A. ;
Burge, Christopher B. .
SCIENCE, 2008, 320 (5883) :1643-1647
[99]   Structural basis for microRNA targeting [J].
Schirle, Nicole T. ;
Sheu-Gruttadauria, Jessica ;
MacRae, Ian J. .
SCIENCE, 2014, 346 (6209) :608-613
[100]   The Crystal Structure of Human Argonaute2 [J].
Schirle, Nicole T. ;
MacRae, Ian J. .
SCIENCE, 2012, 336 (6084) :1037-1040