title: Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1.
abstract: MicroRNAs (miRNAs) play essential, conserved roles in diverse developmental processes through association with the miRNA-induced silencing complex (miRISC). Whereas fundamental insights into the mechanistic framework of miRNA biogenesis and target gene silencing have been established, posttranslational modifications that affect miRISC function are less well understood. Here we report that the conserved serine/threonine kinase, casein kinase II (CK2), promotes miRISC function in Caenorhabditis elegans. CK2 inactivation results in developmental defects that phenocopy loss of miRISC cofactors and enhances the loss of miRNA function in diverse cellular contexts. Whereas CK2 is dispensable for miRNA biogenesis and the stability of miRISC cofactors, it is required for efficient miRISC target mRNA binding and silencing. Importantly, we identify the conserved DEAD-box RNA helicase, CGH-1/DDX6, as a key CK2 substrate within miRISC and demonstrate phosphorylation of a conserved N-terminal serine is required for CGH-1 function in the miRNA pathway.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Amelia F
authors.initials: AF
authors.lastname: Alessi
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Vishal
authors.initials: V
authors.lastname: Khivansara
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Freeberg
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Tu
authors.affiliation: Department of Biology, Central Michigan University, Mount Pleasant, MI 48859.
authors.forename: Eric
authors.initials: E
authors.lastname: Montoye
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Biology, Central Michigan University, Mount Pleasant, MI 48859.
authors.forename: Xantha
authors.initials: X
authors.lastname: Karp
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109; jnkim@jhu.edu.
authors.forename: John K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D012316:RNA Nucleotidyltransferases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D012694:Serine; D047390:Casein Kinase II; D012316:RNA Nucleotidyltransferases; C490618:cgh-1 protein, C elegans; D053487:DEAD-box RNA Helicases
keywords: CGH-1; casein kinase II; miRISC; microRNA; phosphorylation