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The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression
During an immune response to microbial infection, CD8(+) T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8(+) T cell differentiation have been extensively characterized, the role of long noncoding...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127983/ https://www.ncbi.nlm.nih.gov/pubmed/35593887 http://dx.doi.org/10.1084/jem.20211756 |
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author | Kanbar, Jad N. Ma, Shengyun Kim, Eleanor S. Kurd, Nadia S. Tsai, Matthew S. Tysl, Tiffani Widjaja, Christella E. Limary, Abigail E. Yee, Brian He, Zhaoren Hao, Yajing Fu, Xiang-Dong Yeo, Gene W. Huang, Wendy J. Chang, John T. |
author_facet | Kanbar, Jad N. Ma, Shengyun Kim, Eleanor S. Kurd, Nadia S. Tsai, Matthew S. Tysl, Tiffani Widjaja, Christella E. Limary, Abigail E. Yee, Brian He, Zhaoren Hao, Yajing Fu, Xiang-Dong Yeo, Gene W. Huang, Wendy J. Chang, John T. |
author_sort | Kanbar, Jad N. |
collection | PubMed |
description | During an immune response to microbial infection, CD8(+) T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8(+) T cell differentiation have been extensively characterized, the role of long noncoding RNAs (lncRNAs) in this process remains poorly understood. Using a functional genetic knockdown screen, we identified the lncRNA Malat1 as a regulator of terminal effector cells and the terminal effector memory (t-T(EM)) circulating memory subset. Evaluation of chromatin-enriched lncRNAs revealed that Malat1 grouped with trans lncRNAs that exhibit increased RNA interactions at gene promoters and gene bodies. Moreover, we observed that Malat1 was associated with increased H3K27me3 deposition at a number of memory cell-associated genes through a direct interaction with Ezh2, thereby promoting terminal effector and t-T(EM) cell differentiation. Our findings suggest an important functional role of Malat1 in regulating CD8(+) T cell differentiation and broaden the knowledge base of lncRNAs in CD8(+) T cell biology. |
format | Online Article Text |
id | pubmed-9127983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91279832022-11-20 The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression Kanbar, Jad N. Ma, Shengyun Kim, Eleanor S. Kurd, Nadia S. Tsai, Matthew S. Tysl, Tiffani Widjaja, Christella E. Limary, Abigail E. Yee, Brian He, Zhaoren Hao, Yajing Fu, Xiang-Dong Yeo, Gene W. Huang, Wendy J. Chang, John T. J Exp Med Article During an immune response to microbial infection, CD8(+) T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8(+) T cell differentiation have been extensively characterized, the role of long noncoding RNAs (lncRNAs) in this process remains poorly understood. Using a functional genetic knockdown screen, we identified the lncRNA Malat1 as a regulator of terminal effector cells and the terminal effector memory (t-T(EM)) circulating memory subset. Evaluation of chromatin-enriched lncRNAs revealed that Malat1 grouped with trans lncRNAs that exhibit increased RNA interactions at gene promoters and gene bodies. Moreover, we observed that Malat1 was associated with increased H3K27me3 deposition at a number of memory cell-associated genes through a direct interaction with Ezh2, thereby promoting terminal effector and t-T(EM) cell differentiation. Our findings suggest an important functional role of Malat1 in regulating CD8(+) T cell differentiation and broaden the knowledge base of lncRNAs in CD8(+) T cell biology. Rockefeller University Press 2022-05-20 /pmc/articles/PMC9127983/ /pubmed/35593887 http://dx.doi.org/10.1084/jem.20211756 Text en © 2022 Kanbar et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/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 | Article Kanbar, Jad N. Ma, Shengyun Kim, Eleanor S. Kurd, Nadia S. Tsai, Matthew S. Tysl, Tiffani Widjaja, Christella E. Limary, Abigail E. Yee, Brian He, Zhaoren Hao, Yajing Fu, Xiang-Dong Yeo, Gene W. Huang, Wendy J. Chang, John T. The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title | The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title_full | The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title_fullStr | The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title_full_unstemmed | The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title_short | The long noncoding RNA Malat1 regulates CD8(+) T cell differentiation by mediating epigenetic repression |
title_sort | long noncoding rna malat1 regulates cd8(+) t cell differentiation by mediating epigenetic repression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127983/ https://www.ncbi.nlm.nih.gov/pubmed/35593887 http://dx.doi.org/10.1084/jem.20211756 |
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