title: An endogenous small interfering RNA pathway in Drosophila.
abstract: Drosophila 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.
authors.affiliation: Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Czech
authors.forename: Colin D
authors.initials: CD
authors.lastname: Malone
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Alexander
authors.initials: A
authors.lastname: Stark
authors.forename: Catherine
authors.initials: C
authors.lastname: Schlingeheyde
authors.forename: Monica
authors.initials: M
authors.lastname: Dus
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.forename: Julius
authors.initials: J
authors.lastname: Brennecke
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D020365:RNA Helicases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D018626:Retroelements / Q000235:genetics; D043244:Ribonuclease III
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C503213:Loqs protein, Drosophila; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D018626:Retroelements; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases