Selective termination of lncRNA transcription promotes heterochromatin silencing and cell differentiation

Leila Touat-Todeschini, Yuichi Shichino, Mathieu Dangin, Nicolas Thierry-Mieg, Benoit Gilquin, Edwige Hiriart, Ravi Sachidanandam, Emeline Lambert, Janine Brettschneider, Michael Reuter, Jan Kadlec, Ramesh Pillai, Akira Yamashita, Masayuki Yamamoto, André Verdel

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2626-2641
Number of pages16
JournalEMBO Journal
Volume36
Issue number17
DOIs
StatePublished - 1 Sep 2017

Keywords

  • YTH domain
  • heterochromatin
  • non-coding RNA (ncRNA)
  • sexual differentiation
  • transcription

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