Cargando…

Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs

Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complex...

Descripción completa

Detalles Bibliográficos
Autores principales: Thillainadesan, Gobi, Xiao, Hua, Holla, Sahana, Dhakshnamoorthy, Jothy, Jenkins, Lisa M. Miller, Wheeler, David, Grewal, Shiv I. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229227/
https://www.ncbi.nlm.nih.gov/pubmed/32415063
http://dx.doi.org/10.1038/s41467-020-16280-y
_version_ 1783534719489540096
author Thillainadesan, Gobi
Xiao, Hua
Holla, Sahana
Dhakshnamoorthy, Jothy
Jenkins, Lisa M. Miller
Wheeler, David
Grewal, Shiv I. S.
author_facet Thillainadesan, Gobi
Xiao, Hua
Holla, Sahana
Dhakshnamoorthy, Jothy
Jenkins, Lisa M. Miller
Wheeler, David
Grewal, Shiv I. S.
author_sort Thillainadesan, Gobi
collection PubMed
description Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2(ARS2) protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs.
format Online
Article
Text
id pubmed-7229227
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-72292272020-06-05 Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs Thillainadesan, Gobi Xiao, Hua Holla, Sahana Dhakshnamoorthy, Jothy Jenkins, Lisa M. Miller Wheeler, David Grewal, Shiv I. S. Nat Commun Article Long non-coding RNAs (lncRNAs) are components of epigenetic control mechanisms that ensure appropriate and timely gene expression. The functions of lncRNAs are often mediated through associated gene regulatory activities, but how lncRNAs are distinguished from other RNAs and recruit effector complexes is unclear. Here, we utilize the fission yeast Schizosaccharomyces pombe to investigate how lncRNAs engage silencing activities to regulate gene expression in cis. We find that invasion of lncRNA transcription into the downstream gene body incorporates a cryptic intron required for repression of that gene. Our analyses show that lncRNAs containing cryptic introns are targeted by the conserved Pir2(ARS2) protein in association with splicing factors, which recruit RNA processing and chromatin-modifying activities involved in gene silencing. Pir2 and splicing machinery are broadly required for gene repression. Our finding that human ARS2 also interacts with splicing factors suggests a conserved mechanism mediates gene repression through cryptic introns within lncRNAs. Nature Publishing Group UK 2020-05-15 /pmc/articles/PMC7229227/ /pubmed/32415063 http://dx.doi.org/10.1038/s41467-020-16280-y Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Thillainadesan, Gobi
Xiao, Hua
Holla, Sahana
Dhakshnamoorthy, Jothy
Jenkins, Lisa M. Miller
Wheeler, David
Grewal, Shiv I. S.
Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title_full Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title_fullStr Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title_full_unstemmed Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title_short Conserved protein Pir2(ARS2) mediates gene repression through cryptic introns in lncRNAs
title_sort conserved protein pir2(ars2) mediates gene repression through cryptic introns in lncrnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229227/
https://www.ncbi.nlm.nih.gov/pubmed/32415063
http://dx.doi.org/10.1038/s41467-020-16280-y
work_keys_str_mv AT thillainadesangobi conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT xiaohua conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT hollasahana conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT dhakshnamoorthyjothy conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT jenkinslisammiller conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT wheelerdavid conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas
AT grewalshivis conservedproteinpir2ars2mediatesgenerepressionthroughcrypticintronsinlncrnas