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A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma

Correct 3’end processing of mRNAs is one of the regulatory cornerstones of gene expression. In a parasite that must adapt to the regulatory requirements of its multi-host life style, there is a need to adopt additional means to partition the distinct transcriptional signatures of the closely and tan...

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Autores principales: Farhat, Dayana C, Bowler, Matthew W, Communie, Guillaume, Pontier, Dominique, Belmudes, Lucid, Mas, Caroline, Corrao, Charlotte, Couté, Yohann, Bougdour, Alexandre, Lagrange, Thierry, Hakimi, Mohamed-Ali, Swale, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313237/
https://www.ncbi.nlm.nih.gov/pubmed/34263725
http://dx.doi.org/10.7554/eLife.68312
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author Farhat, Dayana C
Bowler, Matthew W
Communie, Guillaume
Pontier, Dominique
Belmudes, Lucid
Mas, Caroline
Corrao, Charlotte
Couté, Yohann
Bougdour, Alexandre
Lagrange, Thierry
Hakimi, Mohamed-Ali
Swale, Christopher
author_facet Farhat, Dayana C
Bowler, Matthew W
Communie, Guillaume
Pontier, Dominique
Belmudes, Lucid
Mas, Caroline
Corrao, Charlotte
Couté, Yohann
Bougdour, Alexandre
Lagrange, Thierry
Hakimi, Mohamed-Ali
Swale, Christopher
author_sort Farhat, Dayana C
collection PubMed
description Correct 3’end processing of mRNAs is one of the regulatory cornerstones of gene expression. In a parasite that must adapt to the regulatory requirements of its multi-host life style, there is a need to adopt additional means to partition the distinct transcriptional signatures of the closely and tandemly arranged stage-specific genes. In this study, we report our findings in T. gondii of an m6A-dependent 3’end polyadenylation serving as a transcriptional barrier at these loci. We identify the core polyadenylation complex within T. gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. We bring evidence of the specificity of this interaction both biochemically, and by determining the crystal structure at high resolution of the T. gondii CPSF4-YTH in complex with an m6A-modified RNA. We show that the loss of m6A, both at the level of its deposition or its recognition is associated with an increase in aberrantly elongated chimeric mRNAs emanating from impaired transcriptional termination, a phenotype previously noticed in the plant model Arabidopsis thaliana. Nanopore direct RNA sequencing shows the occurrence of transcriptional read-through breaching into downstream repressed stage-specific genes, in the absence of either CPSF4 or the m6A RNA methylase components in both T. gondii and A. thaliana. Taken together, our results shed light on an essential regulatory mechanism coupling the pathways of m6A metabolism directly to the cleavage and polyadenylation processes, one that interestingly seem to serve, in both T. gondii and A. thaliana, as a guardian against aberrant transcriptional read-throughs.
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spelling pubmed-83132372021-07-28 A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma Farhat, Dayana C Bowler, Matthew W Communie, Guillaume Pontier, Dominique Belmudes, Lucid Mas, Caroline Corrao, Charlotte Couté, Yohann Bougdour, Alexandre Lagrange, Thierry Hakimi, Mohamed-Ali Swale, Christopher eLife Microbiology and Infectious Disease Correct 3’end processing of mRNAs is one of the regulatory cornerstones of gene expression. In a parasite that must adapt to the regulatory requirements of its multi-host life style, there is a need to adopt additional means to partition the distinct transcriptional signatures of the closely and tandemly arranged stage-specific genes. In this study, we report our findings in T. gondii of an m6A-dependent 3’end polyadenylation serving as a transcriptional barrier at these loci. We identify the core polyadenylation complex within T. gondii and establish CPSF4 as a reader for m6A-modified mRNAs, via a YTH domain within its C-terminus, a feature which is shared with plants. We bring evidence of the specificity of this interaction both biochemically, and by determining the crystal structure at high resolution of the T. gondii CPSF4-YTH in complex with an m6A-modified RNA. We show that the loss of m6A, both at the level of its deposition or its recognition is associated with an increase in aberrantly elongated chimeric mRNAs emanating from impaired transcriptional termination, a phenotype previously noticed in the plant model Arabidopsis thaliana. Nanopore direct RNA sequencing shows the occurrence of transcriptional read-through breaching into downstream repressed stage-specific genes, in the absence of either CPSF4 or the m6A RNA methylase components in both T. gondii and A. thaliana. Taken together, our results shed light on an essential regulatory mechanism coupling the pathways of m6A metabolism directly to the cleavage and polyadenylation processes, one that interestingly seem to serve, in both T. gondii and A. thaliana, as a guardian against aberrant transcriptional read-throughs. eLife Sciences Publications, Ltd 2021-07-15 /pmc/articles/PMC8313237/ /pubmed/34263725 http://dx.doi.org/10.7554/eLife.68312 Text en © 2021, Farhat et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Farhat, Dayana C
Bowler, Matthew W
Communie, Guillaume
Pontier, Dominique
Belmudes, Lucid
Mas, Caroline
Corrao, Charlotte
Couté, Yohann
Bougdour, Alexandre
Lagrange, Thierry
Hakimi, Mohamed-Ali
Swale, Christopher
A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title_full A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title_fullStr A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title_full_unstemmed A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title_short A plant-like mechanism coupling m6A reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in Toxoplasma
title_sort plant-like mechanism coupling m6a reading to polyadenylation safeguards transcriptome integrity and developmental gene partitioning in toxoplasma
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313237/
https://www.ncbi.nlm.nih.gov/pubmed/34263725
http://dx.doi.org/10.7554/eLife.68312
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