A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs

被引：55

作者：

Fulga, Tudor A. ^{[1
,4
]}

McNeill, Elizabeth M. ^{[1
]}

Binari, Richard ^{[2
,3
]}

Yelick, Julia ^{[1
]}

Blanche, Alexandra ^{[1
]}

Booker, Matthew ^{[2
]}

Steinkraus, Bruno R. ^{[4
]}

Schnall-Levin, Michael ^{[2
]}

Zhao, Yong ^{[2
]}

DeLuca, Todd ^{[5
]}

Bejarano, Fernando ^{[6
]}

Han, Zhe ^{[7
]}

Lai, Eric C. ^{[6
]}

Wall, Dennis P. ^{[5
]}

Perrimon, Norbert ^{[2
,3
]}

Van Vactor, David ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Univ Oxford, Weatherall Inst Mol Med, Radcliffe Dept Med, Oxford OX3 9DS, England

[5] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[6] Sloan Kettering Inst, Dept Dev Biol, New York, NY 10065 USA

[7] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

MESSENGER-RNA; TRANSLATIONAL REPRESSION; MUSCLE DIFFERENTIATION; WING DEVELOPMENT; BANTAM MIRNA; EXPRESSION; NEURODEGENERATION; APOPTOSIS; PTEN; LIM;

D O I：

10.1038/ncomms8279

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：

Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4-8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes.

引用

页数：10

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