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RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

Severe coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize...

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Autores principales: Meng, Yuting, Zhang, Qiong, Wang, Kaihang, Zhang, Xujun, Yang, Rongwei, Bi, Kefan, Chen, Wenbiao, Diao, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298984/
https://www.ncbi.nlm.nih.gov/pubmed/34301919
http://dx.doi.org/10.1038/s41419-021-04012-z
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author Meng, Yuting
Zhang, Qiong
Wang, Kaihang
Zhang, Xujun
Yang, Rongwei
Bi, Kefan
Chen, Wenbiao
Diao, Hongyan
author_facet Meng, Yuting
Zhang, Qiong
Wang, Kaihang
Zhang, Xujun
Yang, Rongwei
Bi, Kefan
Chen, Wenbiao
Diao, Hongyan
author_sort Meng, Yuting
collection PubMed
description Severe coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.
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spelling pubmed-82989842021-07-23 RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes Meng, Yuting Zhang, Qiong Wang, Kaihang Zhang, Xujun Yang, Rongwei Bi, Kefan Chen, Wenbiao Diao, Hongyan Cell Death Dis Article Severe coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19. Nature Publishing Group UK 2021-07-23 /pmc/articles/PMC8298984/ /pubmed/34301919 http://dx.doi.org/10.1038/s41419-021-04012-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Meng, Yuting
Zhang, Qiong
Wang, Kaihang
Zhang, Xujun
Yang, Rongwei
Bi, Kefan
Chen, Wenbiao
Diao, Hongyan
RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title_full RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title_fullStr RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title_full_unstemmed RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title_short RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes
title_sort rbm15-mediated n6-methyladenosine modification affects covid-19 severity by regulating the expression of multitarget genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298984/
https://www.ncbi.nlm.nih.gov/pubmed/34301919
http://dx.doi.org/10.1038/s41419-021-04012-z
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