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The RNA exosome nuclease complex regulates human embryonic stem cell differentiation

A defining feature of embryonic stem cells (ESCs) is the ability to differentiate into all three germ layers. Pluripotency is maintained in part by a unique transcription network that maintains expression of pluripotency-specific transcription factors and represses developmental genes. While the mec...

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Autores principales: Belair, Cedric, Sim, Soyeong, Kim, Kun-Yong, Tanaka, Yoshiaki, Park, In-Hyun, Wolin, Sandra L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683745/
https://www.ncbi.nlm.nih.gov/pubmed/31308215
http://dx.doi.org/10.1083/jcb.201811148
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author Belair, Cedric
Sim, Soyeong
Kim, Kun-Yong
Tanaka, Yoshiaki
Park, In-Hyun
Wolin, Sandra L.
author_facet Belair, Cedric
Sim, Soyeong
Kim, Kun-Yong
Tanaka, Yoshiaki
Park, In-Hyun
Wolin, Sandra L.
author_sort Belair, Cedric
collection PubMed
description A defining feature of embryonic stem cells (ESCs) is the ability to differentiate into all three germ layers. Pluripotency is maintained in part by a unique transcription network that maintains expression of pluripotency-specific transcription factors and represses developmental genes. While the mechanisms that establish this transcription network are well studied, little is known of the posttranscriptional surveillance pathways that degrade differentiation-related RNAs. We report that the surveillance pathway mediated by the RNA exosome nuclease complex represses ESC differentiation. Depletion of the exosome expedites differentiation of human ESCs into all three germ layers. LINE-1 retrotransposons and specific miRNAs, lncRNAs, and mRNAs that encode developmental regulators or affect their expression are all bound by the exosome and increase in level upon exosome depletion. The exosome restrains differentiation in part by degrading transcripts encoding FOXH1, a transcription factor crucial for mesendoderm formation. Our studies establish the exosome as a regulator of human ESC differentiation and reveal the importance of RNA decay in maintaining pluripotency.
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spelling pubmed-66837452020-02-05 The RNA exosome nuclease complex regulates human embryonic stem cell differentiation Belair, Cedric Sim, Soyeong Kim, Kun-Yong Tanaka, Yoshiaki Park, In-Hyun Wolin, Sandra L. J Cell Biol Research Articles A defining feature of embryonic stem cells (ESCs) is the ability to differentiate into all three germ layers. Pluripotency is maintained in part by a unique transcription network that maintains expression of pluripotency-specific transcription factors and represses developmental genes. While the mechanisms that establish this transcription network are well studied, little is known of the posttranscriptional surveillance pathways that degrade differentiation-related RNAs. We report that the surveillance pathway mediated by the RNA exosome nuclease complex represses ESC differentiation. Depletion of the exosome expedites differentiation of human ESCs into all three germ layers. LINE-1 retrotransposons and specific miRNAs, lncRNAs, and mRNAs that encode developmental regulators or affect their expression are all bound by the exosome and increase in level upon exosome depletion. The exosome restrains differentiation in part by degrading transcripts encoding FOXH1, a transcription factor crucial for mesendoderm formation. Our studies establish the exosome as a regulator of human ESC differentiation and reveal the importance of RNA decay in maintaining pluripotency. Rockefeller University Press 2019-08-05 2019-07-15 /pmc/articles/PMC6683745/ /pubmed/31308215 http://dx.doi.org/10.1083/jcb.201811148 Text en © 2019 Belair et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Belair, Cedric
Sim, Soyeong
Kim, Kun-Yong
Tanaka, Yoshiaki
Park, In-Hyun
Wolin, Sandra L.
The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title_full The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title_fullStr The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title_full_unstemmed The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title_short The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
title_sort rna exosome nuclease complex regulates human embryonic stem cell differentiation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683745/
https://www.ncbi.nlm.nih.gov/pubmed/31308215
http://dx.doi.org/10.1083/jcb.201811148
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