RRC ID 76000
Author Liao S, Chen X, Xu T, Jin Q, Xu Z, Xu D, Zhou X, Zhu C, Guang S, Feng X.
Title Antisense ribosomal siRNAs inhibit RNA polymerase I-directed transcription in C. elegans.
Journal Nucleic Acids Res
Abstract Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that function in the nucleus. We previously found that erroneous rRNAs induce the generation of antisense ribosomal siRNAs (risiRNAs) which silence the expression of rRNAs via the nuclear RNAi defective (Nrde) pathway. To further understand the biological roles and mechanisms of this class of small regulatory RNAs, we conducted forward genetic screening to identify factors involved in risiRNA generation in Caenorhabditis elegans. We found that risiRNAs accumulated in the RNA exosome mutants. risiRNAs directed the association of NRDE proteins with pre-rRNAs and the silencing of pre-rRNAs. In the presence of risiRNAs, NRDE-2 accumulated in the nucleolus and colocalized with RNA polymerase I. risiRNAs inhibited the transcription elongation of RNA polymerase I by decreasing RNAP I occupancy downstream of the RNAi-targeted site. Meanwhile, exosomes mislocalized from the nucleolus to nucleoplasm in suppressor of siRNA (susi) mutants, in which erroneous rRNAs accumulated. These results established a novel model of rRNA surveillance by combining ribonuclease-mediated RNA degradation with small RNA-directed nucleolar RNAi system.
Volume 49(16)
Pages 9194-9210
Published 2021-9-20
DOI 10.1093/nar/gkab662
PII 6345473
PMID 34365510
PMC PMC8450093
MeSH Animals Caenorhabditis elegans Cell Nucleolus / metabolism DNA-Directed RNA Polymerases / metabolism Exosomes / genetics Exosomes / metabolism Gene Silencing Mutation RNA, Ribosomal / genetics RNA, Ribosomal / metabolism* RNA, Small Interfering / genetics RNA, Small Interfering / metabolism* Transcription Elongation, Genetic*
C.elegans tm6653 tm6844 tm5568