RRC ID 46262
Author Avgousti DC, Palani S, Sherman Y, Grishok A.
Title CSR-1 RNAi pathway positively regulates histone expression in C. elegans.
Journal EMBO J
Abstract Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression.
Volume 31(19)
Pages 3821-32
Published 2012-10-3
DOI 10.1038/emboj.2012.216
PII emboj2012216
PMID 22863779
PMC PMC3463841
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism Gene Dosage Gene Silencing Histones / biosynthesis* Protein Binding RNA Interference / physiology* RNA Replicase / genetics RNA Replicase / metabolism RNA, Messenger / chemistry
IF 9.889
Times Cited 31
C.elegans tm892 tm1217