Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 15, Issue 6, Pages 581-590Publisher
NATURE RESEARCH
DOI: 10.1038/nsmb.1438
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Funding
- NHGRI NIH HHS [U01 HG004261, U01-HG004261, U01 HG004261-01] Funding Source: Medline
- NIGMS NIH HHS [R01-GM083300, R01 GM083300, R01 GM083300-01] Funding Source: Medline
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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.
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