Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster Journal Article
| Authors: | Okamura, K.; Balla, S.; Martin, R.; Liu, N.; Lai, E. C. |
| Article Title: | Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster |
| Abstract: | 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. © 2008 Nature Publishing Group. |
| Keywords: | gene cluster; exon; exons; nonhuman; animals; gene; small interfering rna; rna, small interfering; gene locus; intron; introns; gene function; rna interference; transcription, genetic; animalia; drosophila melanogaster; drosophila proteins; rna helicases; rna-induced silencing complex; biogenesis; argonaute 2 protein; rna, double-stranded; nucleic acid; rna analysis; klarsicht gene; thickveins gene |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 15 |
| Issue: | 6 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2008-06-01 |
| Start Page: | 581 |
| End Page: | 590 |
| Language: | English |
| DOI: | 10.1038/nsmb.1438 |
| PUBMED: | 18500351 |
| PROVIDER: | scopus |
| PMCID: | PMC2713754 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 56" - "Export Date: 17 November 2011" - "CODEN: NSMBC" - "Source: Scopus" |
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