Article abstract

Nature Structural & Molecular Biology 15, 581 - 590 (2008)
Published online: 25 May 2008 | Corrected online: 18 June 2008 | doi:10.1038/nsmb.1438



There is a Corrigendum (September 2008) associated with this Article.

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

Katsutomo Okamura1,2, Sudha Balla1,2, Raquel Martin1, Na Liu1 & Eric C Lai1

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 and, based on previously published small RNA data, 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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  1. Sloan-Kettering Institute, Department of Developmental Biology, 521 Rockefeller Research Laboratories, 1275 York Avenue, Box 252, New York, New York 10065.
  2. These authors contributed equally to this work.

Correspondence to: Eric C Lai1 e-mail: laie@mskcc.org

* In the version of this article initially published, the Abstract did not convey that two conclusions regarding cis-NATs, presented in Table 1, were derived from analysis of previously published data (references 20 and 21 in the paper). The third sentence of the Abstract should read: "First, >100 cis-NATs with overlapping 3' exons generate 21-nt and, based on previously published small RNA data, Dicer-2 (Dcr-2)–dependent, 3'-end modified siRNAs." The correction has been made to the HTML and PDF versions of the article.

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