RRC ID 53482
Author Alessi AF, Khivansara V, Han T, Freeberg MA, Moresco JJ, Tu PG, Montoye E, Yates JR 3rd, Karp X, Kim JK.
Title Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1.
Journal Proc Natl Acad Sci U S A
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.
Volume 112(52)
Pages E7213-22
Published 2015-12-29
DOI 10.1073/pnas.1509499112
PII 1509499112
PMID 26669440
PMC PMC4702986
MeSH Animals Animals, Genetically Modified Blotting, Western Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Casein Kinase II / genetics* Casein Kinase II / metabolism DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism Gene Expression Profiling MicroRNAs / genetics* MicroRNAs / metabolism Oligonucleotide Array Sequence Analysis Phosphorylation Protein Binding RNA Interference* RNA Nucleotidyltransferases / genetics* RNA Nucleotidyltransferases / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism RNA-Induced Silencing Complex / genetics* RNA-Induced Silencing Complex / metabolism Serine / genetics Serine / metabolism Signal Transduction / genetics
IF 9.58
Times Cited 7
C.elegans tm3681 tm369