Large-Scale Identification of MicroRNA Targets in Murine Dgcr8-Deficient Embryonic Stem Cell Lines

被引：9

作者：

Davis, Matthew P. A. ^{[1
,2
]}

Abreu-Goodger, Cei ^{[2
,3
]}

van Dongen, Stijn ^{[2
]}

Lu, Dong ^{[1
]}

Tate, Peri H. ^{[1
]}

Bartonicek, Nenad ^{[2
]}

Kutter, Claudia ^{[4
]}

Liu, Pentao ^{[1
]}

Skarnes, William C. ^{[1
]}

Enright, Anton J. ^{[2
]}

Dunham, Ian ^{[2
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton, England

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

[3] CINVESTAV, Natl Lab Genom Biodivers Langebio, Guanajuato, Mexico

[4] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England

来源：

PLOS ONE | 2012年 / 7卷 / 08期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

RNA-INTERFERENCE; SELF-RENEWAL; MICROPROCESSOR COMPLEX; DROSHA-DGCR8; COMPLEX; MESSENGER-RNAS; GENOME-WIDE; C-ELEGANS; ES CELLS; EXPRESSION; MOUSE;

D O I：

10.1371/journal.pone.0041762

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Small RNAs such as microRNAs play important roles in embryonic stem cell maintenance and differentiation. A broad range of microRNAs is expressed in embryonic stem cells while only a fraction of their targets have been identified. We have performed large-scale identification of embryonic stem cell microRNA targets using a murine embryonic stem cell line deficient in the expression of Dgcr8. These cells are heavily depleted for microRNAs, allowing us to reintroduce specific microRNA duplexes and identify refined target sets. We used deep sequencing of small RNAs, mRNA expression profiling and bioinformatics analysis of microRNA seed matches in 3' UTRs to identify target transcripts. Consequently, we have identified a network of microRNAs that converge on the regulation of several important cellular pathways. Additionally, our experiments have revealed a novel candidate for Dgcr8-independent microRNA genesis and highlighted the challenges currently facing miRNA annotation.

引用

页数：17

共 65 条

[1]

A genome-wide, end-sequenced 129Sv BAC library resource for targeting vector construction [J].

Adams, DJ ;

Quail, MA ;

Cox, T ;

van der Weyden, L ;

Gorick, BD ;

Su, Q ;

Chan, WI ;

Davies, R ;

Bonfield, JK ;

Law, F ;

Humphray, S ;

Plumb, B ;

Liu, PT ;

Rogers, J ;

Bradley, A .

GENOMICS, 2005, 86 (06) :753-758

[2]

Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency [J].

Anokye-Danso, Frederick ;

Trivedi, Chinmay M. ;

Juhr, Denise ;

Gupta, Mudit ;

Cui, Zheng ;

Tian, Ying ;

Zhang, Yuzhen ;

Yang, Wenli ;

Gruber, Peter J. ;

Epstein, Jonathan A. ;

Morrisey, Edward E. .

CELL STEM CELL, 2011, 8 (04) :376-388

[3]

Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs [J].

Babiarz, Joshua E. ;

Ruby, J. Graham ;

Wang, Yangming ;

Bartel, David P. ;

Blelloch, Robert .

GENES & DEVELOPMENT, 2008, 22 (20) :2773-2785

[4]

The impact of microRNAs on protein output [J].

Baek, Daehyun ;

Villen, Judit ;

Shin, Chanseok ;

Camargo, Fernando D. ;

Gygi, Steven P. ;

Bartel, David P. .

NATURE, 2008, 455 (7209) :64-U38

[5]

MicroRNAs: Target Recognition and Regulatory Functions [J].

Bartel, David P. .

CELL, 2009, 136 (02) :215-233

[6]

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells [J].

Calabrese, J. Mauro ;

Seila, Amy C. ;

Yeo, Gene W. ;

Sharp, Phillip A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (46) :18097-18102

[7]

Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells [J].

Card, Deborah A. Greer ;

Hebbar, Pratibha B. ;

Li, Leping ;

Trotter, Kevin W. ;

Komatsu, Yoshihiro ;

Mishina, Yuji ;

Archer, Trevor K. .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (20) :6426-6438

[8]

Pathway Commons, a web resource for biological pathway data [J].

Cerami, Ethan G. ;

Gross, Benjamin E. ;

Demir, Emek ;

Rodchenkov, Igor ;

Babur, Oezguen ;

Anwar, Nadia ;

Schultz, Nikolaus ;

Bader, Gary D. ;

Sander, Chris .

NUCLEIC ACIDS RESEARCH, 2011, 39 :D685-D690

[9]

Mammalian microRNAs: experimental evaluation of novel and previously annotated genes [J].

Chiang, H. Rosaria ;

Schoenfeld, Lori W. ;

Ruby, J. Graham ;

Auyeung, Vincent C. ;

Spies, Noah ;

Baek, Daehyun ;

Johnston, Wendy K. ;

Russ, Carsten ;

Luo, Shujun ;

Babiarz, Joshua E. ;

Blelloch, Robert ;

Schroth, Gary P. ;

Nusbaum, Chad ;

Bartel, David P. .

GENES & DEVELOPMENT, 2010, 24 (10) :992-1009

[10]

Function and regulation of the Mediator complex [J].

Conaway, Ronald C. ;

Conaway, Joan Weliky .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2011, 21 (02) :225-230

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