Institut for Advanced Biosciences, UMR InsermU1209/CNRS5309/UGA, University of Grenoble Alpes, Grenoble, France, Laboratory of Cell Responses, National Institute for Basic Biology, Okazaki, Aichi, Japan, TIMC-IMAG, University of Grenoble Alpes, Grenoble, France, CNRS, TIMC-IMAG, UMR CNRS 5525, Grenoble, France, CEA, LETI, CLINATEC, MINATEC Campus, University of Grenoble Alpes, Grenoble, France, Department of Oncological Sciences, Icahn School of Medicine at Sinai, New York, NY, United States, European Molecular Biology Laboratory, Grenoble Outstation, University of Grenoble Alpes-EMBL-CNRS, Grenoble, France, Unit for Virus Host-Cell Interactions, University of Grenoble Alpes-EMBL-CNRS, Grenoble, France, Institut de Biologie Structurale (IBS), CEA, CNRS, Université Grenoble Alpes, Grenoble, France, Department of Molecular Biology, University of Geneva, Geneva 4, Switzerland, Department of Basic Biology, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, Japan

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. © 2017 The Authors

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

long untranslated RNA, mitogen activated protein kinase kinase kinase, Mmi1 protein, RNA binding protein, unclassified drug, heterochromatin, long untranslated RNA, Schizosaccharomyces pombe protein, Article, cell cycle S phase, cell differentiation, cellular distribution, controlled study, DNA transcription, exosome, gene silencing, heterochromatin, high throughput sequencing, histone methylation, meiosis, nonhuman, priority journal, protein domain, protein RNA binding, RNA degradation, RNA interference, RNA transcription, Schizosaccharomyces pombe, sex differentiation, sporogenesis, transcription termination, yeast cell, gene expression regulation, genetics, heterochromatin, metabolism, physiology, Schizosaccharomyces, Gene Expression Regulation, Fungal, Gene Silencing, Heterochromatin, RNA, Long Noncoding, Schizosaccharomyces, Schizosaccharomyces pombe Proteins