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Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats

Internal RNA modifications have been known for decades, however their roles in mRNA regulation have only recently started to be elucidated. Here we investigated the most abundant mRNA modification, N(6)-methyladenosine (m(6)A) in transcripts from the hippocampus of HIV transgenic (Tg) rats. The dist...

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Autores principales: Fu, Yu, Zorman, Barry, Sumazin, Pavel, Sanna, Pietro Paolo, Repunte-Canonigo, Vez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336335/
https://www.ncbi.nlm.nih.gov/pubmed/30653517
http://dx.doi.org/10.1371/journal.pone.0203566
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author Fu, Yu
Zorman, Barry
Sumazin, Pavel
Sanna, Pietro Paolo
Repunte-Canonigo, Vez
author_facet Fu, Yu
Zorman, Barry
Sumazin, Pavel
Sanna, Pietro Paolo
Repunte-Canonigo, Vez
author_sort Fu, Yu
collection PubMed
description Internal RNA modifications have been known for decades, however their roles in mRNA regulation have only recently started to be elucidated. Here we investigated the most abundant mRNA modification, N(6)-methyladenosine (m(6)A) in transcripts from the hippocampus of HIV transgenic (Tg) rats. The distribution of m(6)A peaks within HIV transcripts in HIV Tg rats largely corresponded to the ones observed for HIV transcripts in cell lines and T cells. Host transcripts were found to be differentially m(6)A methylated in HIV Tg rats. The functional roles of the differentially m(6)A methylated pathways in HIV Tg rats is consistent with a key role of RNA methylation in the regulation of the brain transcriptome in chronic HIV disease. In particular, host transcripts show significant differential m(6)A methylation of genes involved in several pathways related to neural function, suggestive of synaptodendritic injury and neurodegeneration, inflammation and immune response, as well as RNA processing and metabolism, such as splicing. Changes in m(6)A methylation were usually positively correlated with differential expression, while differential m(6)A methylation of pathways involved in RNA processing were more likely to be negatively correlated with gene expression changes. Thus, sets of differentially m(6)A methylated, functionally-related transcripts appear to be involved in coordinated transcriptional responses in the context of chronic HIV. Altogether, our results support that m(6)A methylation represents an additional layer of regulation of HIV and host gene expression in vivo that contributes significantly to the transcriptional effects of chronic HIV.
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spelling pubmed-63363352019-01-30 Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats Fu, Yu Zorman, Barry Sumazin, Pavel Sanna, Pietro Paolo Repunte-Canonigo, Vez PLoS One Research Article Internal RNA modifications have been known for decades, however their roles in mRNA regulation have only recently started to be elucidated. Here we investigated the most abundant mRNA modification, N(6)-methyladenosine (m(6)A) in transcripts from the hippocampus of HIV transgenic (Tg) rats. The distribution of m(6)A peaks within HIV transcripts in HIV Tg rats largely corresponded to the ones observed for HIV transcripts in cell lines and T cells. Host transcripts were found to be differentially m(6)A methylated in HIV Tg rats. The functional roles of the differentially m(6)A methylated pathways in HIV Tg rats is consistent with a key role of RNA methylation in the regulation of the brain transcriptome in chronic HIV disease. In particular, host transcripts show significant differential m(6)A methylation of genes involved in several pathways related to neural function, suggestive of synaptodendritic injury and neurodegeneration, inflammation and immune response, as well as RNA processing and metabolism, such as splicing. Changes in m(6)A methylation were usually positively correlated with differential expression, while differential m(6)A methylation of pathways involved in RNA processing were more likely to be negatively correlated with gene expression changes. Thus, sets of differentially m(6)A methylated, functionally-related transcripts appear to be involved in coordinated transcriptional responses in the context of chronic HIV. Altogether, our results support that m(6)A methylation represents an additional layer of regulation of HIV and host gene expression in vivo that contributes significantly to the transcriptional effects of chronic HIV. Public Library of Science 2019-01-17 /pmc/articles/PMC6336335/ /pubmed/30653517 http://dx.doi.org/10.1371/journal.pone.0203566 Text en © 2019 Fu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fu, Yu
Zorman, Barry
Sumazin, Pavel
Sanna, Pietro Paolo
Repunte-Canonigo, Vez
Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title_full Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title_fullStr Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title_full_unstemmed Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title_short Epitranscriptomics: Correlation of N(6)-methyladenosine RNA methylation and pathway dysregulation in the hippocampus of HIV transgenic rats
title_sort epitranscriptomics: correlation of n(6)-methyladenosine rna methylation and pathway dysregulation in the hippocampus of hiv transgenic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336335/
https://www.ncbi.nlm.nih.gov/pubmed/30653517
http://dx.doi.org/10.1371/journal.pone.0203566
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