TY - JOUR
T1 - Bases of antisense lncRNA-associated regulation of gene expression in fission yeast
AU - Wery, Maxime
AU - Gautier, Camille
AU - Descrimes, Marc
AU - Yoda, Mayuko
AU - Migeot, Valérie
AU - Hermand, Damien
AU - Morillon, Antonin
N1 - Funding Information:
AM’s lab is supported by the Agence Nationale de la Recherche (‘REGULncRNA’ and ‘DNA-Life’ grants) and the European Research Council (‘EpincRNA’ starting grant and ‘DARK’ consolidator grants). This work was also supported by grants FNRS-PDR T.0012.14, FNRS-CDR J.0066.16 to DH. DH is a senior FNRS Research Associate. This work has benefited from the facilities and expertise of the NGS platform of Institut Curie, supported by the Agence Nationale de la Recherche (ANR-10-EQPX-03, ANR10-INBS-09-08) and the Canceropôle Ile-de-France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank Fred Winston for the Set2-Myc strain and Danesh Moazed for the dcr1 OE vector. We also thank Thomas Rio Frio, Sylvain Baulande, Patricia Legoix-Né and Virginie Raynal (NGS platform, Institut Curie). We are grateful to Nicolas Vogt and Ugo Szachnowski for assistance. We thank all the members of our labs for discussions and critical reading of the manuscript.
Publisher Copyright:
© 2018 Wery et al. http://creativecommons.org/licenses/by/4.0/.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - Antisense (as)lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear. Using Native Elongating Transcript sequencing, here we show that stabilization of antisense Exo2-sensitivite lncRNAs (XUTs) results in the attenuation, at the nascent transcription level, of a subset of highly expressed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation. Mechanistic investigations on the catalase gene ctt1 revealed that its induction following oxidative stress is impaired in Exo2-deficient cells, correlating with the accumulation of an asXUT. Interestingly, expression of this asXUT was also activated in wild-type cells upon oxidative stress, concomitant to ctt1 induction, indicating a potential attenuation feedback. This attenuation correlates with asXUT abundance, it is transcriptional, characterized by low RNAPII-ser5 phosphorylation, and it requires an histone deacetylase activity and the conserved Set2 histone methyltransferase. Finally, we identified Dicer as another RNA processing factor acting on ctt1 induction, but independently of Exo2. We propose that asXUTs could modulate the expression of their paired-sense genes when it exceeds a critical threshold, using a conserved mechanism independent of RNAi.
AB - Antisense (as)lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear. Using Native Elongating Transcript sequencing, here we show that stabilization of antisense Exo2-sensitivite lncRNAs (XUTs) results in the attenuation, at the nascent transcription level, of a subset of highly expressed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation. Mechanistic investigations on the catalase gene ctt1 revealed that its induction following oxidative stress is impaired in Exo2-deficient cells, correlating with the accumulation of an asXUT. Interestingly, expression of this asXUT was also activated in wild-type cells upon oxidative stress, concomitant to ctt1 induction, indicating a potential attenuation feedback. This attenuation correlates with asXUT abundance, it is transcriptional, characterized by low RNAPII-ser5 phosphorylation, and it requires an histone deacetylase activity and the conserved Set2 histone methyltransferase. Finally, we identified Dicer as another RNA processing factor acting on ctt1 induction, but independently of Exo2. We propose that asXUTs could modulate the expression of their paired-sense genes when it exceeds a critical threshold, using a conserved mechanism independent of RNAi.
KW - Acetylation
KW - Catalase/genetics
KW - Endoribonucleases/metabolism
KW - Exodeoxyribonucleases/genetics
KW - Gene Expression Regulation, Fungal
KW - Histone-Lysine N-Methyltransferase/genetics
KW - Oxidative Stress/genetics
KW - Promoter Regions, Genetic
KW - RNA Interference
KW - RNA, Antisense/metabolism
KW - RNA, Fungal/metabolism
KW - RNA, Long Noncoding/metabolism
KW - Schizosaccharomyces/genetics
KW - Schizosaccharomyces pombe Proteins/genetics
KW - Transcription, Genetic/genetics
UR - http://www.scopus.com/inward/record.url?scp=85050967146&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1007465
DO - 10.1371/journal.pgen.1007465
M3 - Article
C2 - 29975684
SN - 1553-7390
VL - 14
SP - e1007465
JO - PLoS Genetics
JF - PLoS Genetics
IS - 7
M1 - e1007465
ER -