論文 - 詳細
| RRC ID | 76059 |
|---|---|
| 著者 | Shukla A, Perales R, Kennedy S. |
| タイトル | piRNAs coordinate poly(UG) tailing to prevent aberrant and perpetual gene silencing. |
| ジャーナル | 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. |
| 巻・号 | 31(20) |
| ページ | 4473-4485.e3 |
| 公開日 | 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 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm872 tm1094 tm1396 |