期刊
EMBO JOURNAL
卷 36, 期 17, 页码 2626-2641出版社
WILEY
DOI: 10.15252/embj.201796571
关键词
heterochromatin; non-coding RNA (ncRNA); sexual differentiation; transcription; YTH domain
资金
- Association pour la Recherche sur le Cancer (ARC)
- JSPS KAKENHI [15H04333]
- Naito Foundation
- Sumitomo Foundation [140283]
- Institut National de la Sante Et de la Recherche Medicale (INSERM) Avenir program
- European Research Council (ERC) Starting Grant [ERC-StG-RNAiEpiMod-210896]
- RNAgermSilence ANR grant
- Grants-in-Aid for Scientific Research [15H04333] Funding Source: KAKEN
Long non-coding RNAs (lncRNAs) regulating gene expression at the chromatin level are widespread among eukaryotes. However, their functions and the mechanisms by which they act are not fully understood. Here, we identify new fission yeast regulatory lncRNAs that are targeted, at their site of transcription, by the YTH domain of the RNA-binding protein Mmi1 and degraded by the nuclear exosome. We uncover that one of them, nam1, regulates entry into sexual differentiation. Importantly, we demonstrate that Mmi1 binding to this lncRNA not only triggers its degradation but also mediates its transcription termination, thus preventing lncRNA transcription from invading and repressing the downstream gene encoding a mitogen-activated protein kinase kinase kinase (MAPKKK) essential to sexual differentiation. In addition, we show that Mmi1-mediated termination of lncRNA transcription also takes place at pericentromeric regions where it contributes to heterochromatin gene silencing together with RNA interference (RNAi). These findings reveal an important role for selective termination of lncRNA transcription in both euchromatic and heterochromatic lncRNA-based gene silencing processes.
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