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YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells
N(6)-methyladenosine (m(6)A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m(6)A-specific RNA binding proteins. Despite accumulating evidence that m(6)A plays an important role in modulating pluripotency, the influence of m(6)A reader proteins in plu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266156/ https://www.ncbi.nlm.nih.gov/pubmed/32169943 http://dx.doi.org/10.1261/rna.073502.119 |
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author | Heck, Adam M. Russo, Joseph Wilusz, Jeffrey Nishimura, Erin Osborne Wilusz, Carol J. |
author_facet | Heck, Adam M. Russo, Joseph Wilusz, Jeffrey Nishimura, Erin Osborne Wilusz, Carol J. |
author_sort | Heck, Adam M. |
collection | PubMed |
description | N(6)-methyladenosine (m(6)A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m(6)A-specific RNA binding proteins. Despite accumulating evidence that m(6)A plays an important role in modulating pluripotency, the influence of m(6)A reader proteins in pluripotency is less clear. Here, we report that YTHDF2, an m(6)A reader associated with mRNA degradation, is highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. Through RNA sequencing, we identified a group of m(6)A-modified transcripts associated with neural development that are directly regulated by YTDHF2. Depletion of YTHDF2 in iPSCs leads to stabilization of these transcripts, loss of pluripotency, and induction of neural-specific gene expression. Collectively, our results suggest YTHDF2 functions to restrain expression of neural-specific mRNAs in iPSCs and facilitate their rapid and coordinated up-regulation during neural induction. These effects are both achieved by destabilization of the targeted transcripts. |
format | Online Article Text |
id | pubmed-7266156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72661562021-06-01 YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells Heck, Adam M. Russo, Joseph Wilusz, Jeffrey Nishimura, Erin Osborne Wilusz, Carol J. RNA Article N(6)-methyladenosine (m(6)A) is an abundant post-transcriptional modification that can impact RNA fate via interactions with m(6)A-specific RNA binding proteins. Despite accumulating evidence that m(6)A plays an important role in modulating pluripotency, the influence of m(6)A reader proteins in pluripotency is less clear. Here, we report that YTHDF2, an m(6)A reader associated with mRNA degradation, is highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. Through RNA sequencing, we identified a group of m(6)A-modified transcripts associated with neural development that are directly regulated by YTDHF2. Depletion of YTHDF2 in iPSCs leads to stabilization of these transcripts, loss of pluripotency, and induction of neural-specific gene expression. Collectively, our results suggest YTHDF2 functions to restrain expression of neural-specific mRNAs in iPSCs and facilitate their rapid and coordinated up-regulation during neural induction. These effects are both achieved by destabilization of the targeted transcripts. Cold Spring Harbor Laboratory Press 2020-06 /pmc/articles/PMC7266156/ /pubmed/32169943 http://dx.doi.org/10.1261/rna.073502.119 Text en © 2020 Heck et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Article Heck, Adam M. Russo, Joseph Wilusz, Jeffrey Nishimura, Erin Osborne Wilusz, Carol J. YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title | YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title_full | YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title_fullStr | YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title_full_unstemmed | YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title_short | YTHDF2 destabilizes m(6)A-modified neural-specific RNAs to restrain differentiation in induced pluripotent stem cells |
title_sort | ythdf2 destabilizes m(6)a-modified neural-specific rnas to restrain differentiation in induced pluripotent stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266156/ https://www.ncbi.nlm.nih.gov/pubmed/32169943 http://dx.doi.org/10.1261/rna.073502.119 |
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