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

Autor: Lucid Belmudes, Guillaume Communie, Dayana C. Farhat, Thierry Lagrange, Alexandre Bougdour, Dominique Pontier, Yohann Couté, Matthew W. Bowler, Charlotte Corrao, Christopher Swale, Mohamed-Ali Hakimi, Caroline Mas
Přispěvatelé: Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire européen de biologie moléculaire - European Molecular Biology Laboratory (EMBL Grenoble), European Molecular Biology Laboratory [Grenoble] (EMBL), Institut Laue-Langevin (ILL), ILL, Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Etude de la dynamique des protéomes (EDyP), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Integrated Structural Biology Grenoble (ISBG - UMS 3518 ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-10-INSB-0801 ProFI ANR-10-INSB-0801, ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-18-CE15-0023,HostQuest,Stratégies de Persistence de Toxoplasma gondii : Conquérir la Cellule Hôte et Echapper à la Réponse Immune Innée(2018), ANR-10-LABX-0041,TULIP,Towards a Unified theory of biotic Interactions: the roLe of environmental(2010), ANR-18-EURE-0019,TULIP-GSR,The Toulouse-Perpignan(2018), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Rosalie, Martin, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Stratégies de Persistence de Toxoplasma gondii : Conquérir la Cellule Hôte et Echapper à la Réponse Immune Innée - - HostQuest2018 - ANR-18-CE15-0023 - AAPG2018 - VALID, Towards a Unified theory of biotic Interactions: the roLe of environmental - - TULIP2010 - ANR-10-LABX-0041 - LABX - VALID, The Toulouse-Perpignan - - TULIP-GSR2018 - ANR-18-EURE-0019 - EURE - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Models
Molecular
Polyadenylation
Arabidopsis thaliana
Arabidopsis
Transcriptome
0302 clinical medicine
Gene expression
Biology (General)
0303 health sciences
Microbiology and Infectious Disease
Membrane Glycoproteins
biology
General Neuroscience
Cleavage And Polyadenylation Specificity Factor
Zinc Fingers
General Medicine
Phenotype
epitranscriptomic
Cell biology
EPITRANSCRIPTOMIC MODIFICATIONS
Medicine
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
RNA Splicing Factors
Toxoplasma
[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Research Article
QH301-705.5
Science
Toxoplasma gondii
Nerve Tissue Proteins
M6A
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Humans
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Genes
Developmental
RNA
Messenger
YTH DOMAIN
Gene
030304 developmental biology
Binding Sites
General Immunology and Microbiology
Sequence Analysis
RNA
RNA
Methyltransferases
biology.organism_classification
RNA processing
Gene Expression Regulation
Reading
Other
030217 neurology & neurosurgery
Zdroj: 'eLife ', vol: 10, pages: e68312-1-e68312-37 (2021)
eLife
eLife, eLife Sciences Publication, 2021, 10, pp.e68312. ⟨10.7554/elife.68312⟩
eLife, 2021, 10, pp.e68312. ⟨10.7554/elife.68312⟩
eLife, Vol 10 (2021)
ISSN: 2050-084X
DOI: 10.7554/elife.68312⟩
Popis: 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.
Databáze: OpenAIRE
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