title: Requirement for CRIF1 in RNA interference and Dicer-2 stability.
abstract: RNA interference (RNAi) is a eukaryotic gene-silencing system. Although the biochemistry of RNAi is relatively well defined, how this pathway is regulated remains incompletely understood. To identify genes involved in regulating the RNAi pathway, we screened for genetic mutations in Drosophila that alter the efficiency of RNAi. We identified the Drosophila homolog of the mammalian CR6-interacting factor 1 (CRIF1), also known as growth arrest and DNA-damage-inducible 45-gamma interacting protein (Gadd45GIP1), as a potential new regulator of the RNAi pathway. Loss-of-function mutants of Drosophila CRIF1 (dCRIF) are deficient in RNAi-mediated target gene knock-down, in the biogenesis of small interfering RNA (siRNA) molecules, and in antiviral immunity. Moreover, we show that dCRIF may function by interacting with, and stabilizing, the RNase III enzyme Dicer-2. Our results suggest that dCRIF may play an important role in regulating the RNAi pathway.
authors.affiliation: a Department of Medicine ; University of California San Diego ; La Jolla , CA USA.
authors.forename: Su Jun
authors.initials: SJ
authors.lastname: Lim
authors.forename: Anthony
authors.initials: A
authors.lastname: Scott
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Xiong
authors.forename: Shabnam
authors.initials: S
authors.lastname: Vahidpour
authors.forename: John
authors.initials: J
authors.lastname: Karijolich
authors.forename: Dongdong
authors.initials: D
authors.lastname: Guo
authors.forename: Shanshan
authors.initials: S
authors.lastname: Pei
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Willis X
authors.initials: WX
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D060565:Argonaute Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C116498:piwi protein, Drosophila; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases
keywords: CRIF1, Cytokine response 6 (CR6)-interacting factor 1; Dcr-2, RNAase III enzyme Dicer-2; Drosophila, RNAi, Dcr-2, Gadd45GIP; Gadd45GIP1, growth arrest and DNA-damageinducible 45-gamma interacting protein 1