RRC ID 76059
Author Shukla A, Perales R, Kennedy S.
Title piRNAs coordinate poly(UG) tailing to prevent aberrant and perpetual gene silencing.
Journal Curr Biol
Abstract Noncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of such RNA-directed TEI is the inheritance of gene-silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent indefinite RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than 5 years and hundreds of generations. This perpetual gene silencing is mediated by continuous pUG RNA/siRNA cycling. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of continual and irreversible epigenetic silencing also mediated by continuous maintenance of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.
Volume 31(20)
Pages 4473-4485.e3
Published 2021-10-25
DOI 10.1016/j.cub.2021.07.076
PII S0960-9822(21)01066-6
PMID 34428467
PMC PMC9067611
MeSH Animals Argonaute Proteins / genetics Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Gene Silencing RNA Interference RNA, Double-Stranded / metabolism RNA, Messenger / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism
Resource
C.elegans tm872 tm1094 tm1396