title: Comparative analysis of argonaute-dependent small RNA pathways in Drosophila.
abstract: The specificity of RNAi pathways is determined by several classes of small RNAs, which include siRNAs, piRNAs, endo-siRNAs, and microRNAs (miRNAs). These small RNAs are invariably incorporated into large Argonaute (Ago)-containing effector complexes known as RNA-induced silencing complexes (RISCs), which they guide to silencing targets. Both genetic and biochemical strategies have yielded conserved molecular components of small RNA biogenesis and effector machineries. However, given the complexity of these pathways, there are likely to be additional components and regulators that remain to be uncovered. We have undertaken a comparative and comprehensive RNAi screen to identify genes that impact three major Ago-dependent small RNA pathways that operate in Drosophila S2 cells. We identify subsets of candidates that act positively or negatively in siRNA, endo-siRNA, and miRNA pathways. Our studies indicate that many components are shared among all three Argonaute-dependent silencing pathways, though each is also impacted by discrete sets of genes.
authors.affiliation: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hotta
authors.forename: Ahmet M
authors.initials: AM
authors.lastname: Denli
authors.forename: Pengyu
authors.initials: P
authors.lastname: Hong
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D002460:Cell Line; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D020868:Gene Silencing; D017344:Genes, Insect; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*
chemical_list: C489654:AGO1 protein, Drosophila; C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D034743:RNA-Induced Silencing Complex