Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster

被引：135

作者：

Okamura, Katsutomo ^{[1
]}

Balla, Sudha ^{[1
]}

Martin, Raquel ^{[1
]}

Liu, Na ^{[1
]}

Lai, Eric C. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Dev Biol, New York, NY 10065 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 06期

关键词：

D O I：

10.1038/nsmb.1438

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：

Cis-natural antisense transcripts (cis-NATs) have been speculated to be substrates for endogenous RNA interference (RNAi), but little experimental evidence for such a pathway in animals has been reported. Analysis of massive Drosophila melanogaster small RNA data sets now reveals two mechanisms that yield endogenous small interfering RNAs (siRNAs) via bidirectional transcription. First, > 100 cis-NATs with overlapping 3' exons generate 21-nt, Dicer-2 (Dcr-2)-dependent, 3'-end modified siRNAs. The processing of cis-NATs by RNA interference (RNAi) seems to be actively restricted, and the selected loci are enriched for nucleic acid-based functions and include Argonaute-2 (AGO2) itself. Second, we report that extended intervals of the thickveins and klarsicht genes generate exceptionally abundant siRNAs from both strands. These siRNA clusters derive from atypical cis-NAT arrangements involving introns and 5' or internal exons, but their biogenesis is similarly Dcr-2- and AGO2-dependent. These newly recognized siRNA pathways broaden the scope of regulatory networks mediated by small RNAs.

引用

页码：581 / 590

页数：10

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