RRC ID 46162
著者 Massirer KB, Perez SG, Mondol V, Pasquinelli AE.
タイトル The miR-35-41 family of microRNAs regulates RNAi sensitivity in Caenorhabditis elegans.
ジャーナル PLoS Genet
Abstract RNA interference (RNAi) utilizes small interfering RNAs (siRNAs) to direct silencing of specific genes through transcriptional and post-transcriptional mechanisms. The siRNA guides can originate from exogenous (exo-RNAi) or natural endogenous (endo-RNAi) sources of double-stranded RNA (dsRNA). In Caenorhabditis elegans, inactivation of genes that function in the endo-RNAi pathway can result in enhanced silencing of genes targeted by siRNAs from exogenous sources, indicating cross-regulation between the pathways. Here we show that members of another small RNA pathway, the mir-35-41 cluster of microRNAs (miRNAs) can regulate RNAi. In worms lacking miR-35-41, there is reduced expression of lin-35/Rb, the C. elegans homolog of the tumor suppressor Retinoblastoma gene, previously shown to regulate RNAi responsiveness. Genome-wide microarray analyses show that targets of endo-siRNAs are up-regulated in mir-35-41 mutants, a phenotype also displayed by lin-35/Rb mutants. Furthermore, overexpression of lin-35/Rb specifically rescues the RNAi hypersensitivity of mir-35-41 mutants. Although the mir-35-41 miRNAs appear to be exclusively expressed in germline and embryos, their effect on RNAi sensitivity is transmitted to multiple tissues and stages of development. Additionally, we demonstrate that maternal contribution of miR-35-41 or lin-35/Rb is sufficient to reduce RNAi effectiveness in progeny worms. Our results reveal that miRNAs can broadly regulate other small RNA pathways and, thus, have far reaching effects on gene expression beyond directly targeting specific mRNAs.
巻・号 8(3)
ページ e1002536
公開日 2012-1-1
DOI 10.1371/journal.pgen.1002536
PII PGENETICS-D-11-02011
PMID 22412382
PMC PMC3297572
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Embryonic Development / genetics Gene Expression Regulation, Developmental Gene Silencing Germ Cells / metabolism MicroRNAs* / genetics MicroRNAs* / metabolism RNA Interference* RNA, Double-Stranded / genetics Repressor Proteins* / genetics Repressor Proteins* / metabolism Sequence Deletion Tissue Distribution
IF 5.175
引用数 22
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm1860