Czech, BenjaminMalone, Colin D.Zhou, RuiStark, AlexanderSchlingeheyde, CatherineDus, MonicaPerrimon, NorbertKellis, ManolisWohlschlegel, James A.Sachidanandam, RaviHannon, Gregory J.Brennecke, Julius2021-09-302008-06-05Czech, Benjamin, Colin D. Malone, Rui Zhou, Alexander Stark, Catherine Schlingeheyde, Monica Dus, Norbert Perrimon et al. "An Endogenous Small Interfering RNA Pathway in Drosophila." Nature 453, no. 7196 (2008): 798-802. DOI: 10.1038/nature070070028-08361476-4687https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369628Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of approximately 22 nucleotides in length, which arise from structured precursors through the action of Drosha-Pasha and Dicer-1-Loquacious complexes. These join Argonaute-1 to regulate gene expression. A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons. Piwi-interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi-catalysed cleavage of single-stranded RNAs. Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious rather than the canonical Dicer-2 partner, R2D2 (ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join Argonaute-2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles.en-USResearch Subject Categories::NATURAL SCIENCES::Chemistry::Biochemistry::Functional genomicsJournal Article2021-09-3010.1038/nature07007