title: MicroRNAs mediate gene silencing via multiple different pathways in drosophila.
abstract: MicroRNAs (miRNAs) guide RNA-induced silencing complex (RISC) that contains an Argonaute family protein to complementary target messenger RNAs (mRNAs). Via RISC, miRNAs silence the expression of target mRNAs by shortening the poly(A) tail-which leads to mRNA decay-and by repressing translation. It has been suggested that GW182, an Argonaute-associating protein, plays the central role in such microRNA actions. Here we show that, although GW182 is obligatory for poly(A) shortening, translational repression by microRNAs occurs even in the absence of GW182. Yet, GW182 is also capable of inducing translational repression independently. Both of these translational repression mechanisms block formation of 48S and 80S ribosomal complexes. Thus microRNAs utilize at least three distinct silencing pathways: GW182-mediated deadenylation and GW182-dependent and -independent repression of early translation initiation. Differential contribution from these multiple pathways may explain previous, apparently contradictory observations of how microRNAs inhibit protein synthesis.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukaya
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Tomari
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics*; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D010442:Peptide Chain Initiation, Translational; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D020871:RNA Stability; D034743:RNA-Induced Silencing Complex; D012260:Ribonucleases / Q000378:metabolism
chemical_list: C489654:AGO1 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C513405:Gw protein, Drosophila; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D049410:Luciferases, Renilla; D039601:Eukaryotic Initiation Factor-4A; C501437:CCR4 protein, Drosophila; D012260:Ribonucleases