TY - JOUR
T1 - Selective termination of lncRNA transcription promotes heterochromatin silencing and cell differentiation
AU - Touat-Todeschini, Leila
AU - Shichino, Yuichi
AU - Dangin, Mathieu
AU - Thierry-Mieg, Nicolas
AU - Gilquin, Benoit
AU - Hiriart, Edwige
AU - Sachidanandam, Ravi
AU - Lambert, Emeline
AU - Brettschneider, Janine
AU - Reuter, Michael
AU - Kadlec, Jan
AU - Pillai, Ramesh
AU - Yamashita, Akira
AU - Yamamoto, Masayuki
AU - Verdel, André
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - YTH domain
KW - heterochromatin
KW - non-coding RNA (ncRNA)
KW - sexual differentiation
KW - transcription
UR - http://www.scopus.com/inward/record.url?scp=85026528715&partnerID=8YFLogxK
U2 - 10.15252/embj.201796571
DO - 10.15252/embj.201796571
M3 - Article
C2 - 28765164
AN - SCOPUS:85026528715
SN - 0261-4189
VL - 36
SP - 2626
EP - 2641
JO - EMBO Journal
JF - EMBO Journal
IS - 17
ER -