The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs

被引:296
作者
Okamura, Katsutomo [1 ]
Chung, Wei-Jen [1 ]
Ruby, J. Graham [2 ,3 ,4 ]
Guo, Huili [2 ,3 ,4 ]
Bartel, David P. [2 ,3 ,4 ]
Lai, Eric C. [1 ]
机构
[1] Sloan Kettering Inst, Dept Dev Biol, Rockefeller Res Labs 521, New York, NY 10065 USA
[2] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA
[3] MIT, Dept Biol, Cambridge, MA 02142 USA
[4] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
关键词
D O I
10.1038/nature07015
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
In contrast to microRNAs and Piwi- associated RNAs, short interfering RNAs ( siRNAs) are seemingly dispensable for host- directed gene regulation in Drosophila. This notion is based on the fact that mutants lacking the core siRNA- generating enzyme Dicer- 2 or the predominant siRNA effector Argonaute 2 are viable, fertile and of relatively normal morphology(1,2). Moreover, endogenous Drosophila siRNAs have not yet been identified. Here we report that siRNAs derived from long hairpin RNA genes ( hpRNAs) programme Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors ( Dicer- 2, Hen1 ( known as CG12367) and Argonaute 2) with a canonical microRNA factor ( Loquacious) to generate similar to 21- nucleotide siRNAs. These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila.
引用
收藏
页码:803 / U8
页数:5
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