title: The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.
abstract: In contrast to microRNAs and Piwi-associated RNAs, short interfering RNAs (siRNAs) are seemingly dispensable for host-directed gene regulation in Drosophila. This notion is based on the fact that mutants lacking the core siRNA-generating enzyme Dicer-2 or the predominant siRNA effector Argonaute 2 are viable, fertile and of relatively normal morphology. Moreover, endogenous Drosophila siRNAs have not yet been identified. Here we report that siRNAs derived from long hairpin RNA genes (hpRNAs) programme Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors (Dicer-2, Hen1 (known as CG12367) and Argonaute 2) with a canonical microRNA factor (Loquacious) to generate approximately 21-nucleotide siRNAs. These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila.
authors.affiliation: Sloan-Kettering Institute, Department of Developmental Biology, 521 Rockefeller Research Laboratories, 1275 York Avenue, Box 252, New York, New York 10065, USA.
authors.forename: Katsutomo
authors.initials: K
authors.lastname: Okamura
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chung
authors.forename: J Graham
authors.initials: JG
authors.lastname: Ruby
authors.forename: Huili
authors.initials: H
authors.lastname: Guo
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C503213:Loqs protein, Drosophila; D035683:MicroRNAs; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; C521948:Hen1 protein, Drosophila; D008780:Methyltransferases; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases