Insights into the conservation and diversification of the molecular functions of YTHDF proteins

YT521-B homology (YTH) domain proteins act as readers of N6-methyladenosine (m6A) in mRNA. Members of the YTHDF clade determine properties of m6A-containing mRNAs in the cytoplasm. Vertebrates encode three YTHDF proteins whose possible functional specialization is debated. In land plants, the YTHDF...

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Autores: Flores-Téllez, Daniel, Tankmar, Mathias Due, von Bülow, Sören, Chen, Junyu, Lindorff-Larsen, Kresten, Brodersen, Peter, Arribas-Hernández, Laura
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/378900
Acceso en línea:http://hdl.handle.net/10261/378900
https://api.elsevier.com/content/abstract/scopus_id/85174361857
Access Level:acceso abierto
Palabra clave:YTHDF proteins
Insights
molecular functions
diversification
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spelling Insights into the conservation and diversification of the molecular functions of YTHDF proteinsFlores-Téllez, DanielTankmar, Mathias Duevon Bülow, SörenChen, JunyuLindorff-Larsen, KrestenBrodersen, PeterArribas-Hernández, LauraYTHDF proteinsInsightsmolecular functionsdiversificationYT521-B homology (YTH) domain proteins act as readers of N6-methyladenosine (m6A) in mRNA. Members of the YTHDF clade determine properties of m6A-containing mRNAs in the cytoplasm. Vertebrates encode three YTHDF proteins whose possible functional specialization is debated. In land plants, the YTHDF clade has expanded from one member in basal lineages to eleven so-called EVOLUTIONARILY CONSERVED C-TERMINAL REGION1-11 (ECT1-11) proteins in Arabidopsis thaliana, named after the conserved YTH domain placed behind a long N-terminal intrinsically disordered region (IDR). ECT2, ECT3 and ECT4 show genetic redundancy in stimulation of primed stem cell division, but the origin and implications of YTHDF expansion in higher plants are unknown, as it is unclear whether it involves acquisition of fundamentally different molecular properties, in particular of their divergent IDRs. Here, we use functional complementation of ect2/ect3/ect4 mutants to test whether different YTHDF proteins can perform the same function when similarly expressed in leaf primordia. We show that stimulation of primordial cell division relies on an ancestral molecular function of the m6A-YTHDF axis in land plants that is present in bryophytes and is conserved over YTHDF diversification, as it appears in all major clades of YTHDF proteins in flowering plants. Importantly, although our results indicate that the YTH domains of all arabidopsis ECT proteins have m6A-binding capacity, lineage-specific neo-functionalization of ECT1, ECT9 and ECT11 happened after late duplication events, and involves altered properties of both the YTH domains, and, especially, of the IDRs. We also identify two biophysical properties recurrent in IDRs of YTHDF proteins able to complement ect2 ect3 ect4 mutants, a clear phase separation propensity and a charge distribution that creates electric dipoles. Human and fly YTHDFs do not have IDRs with this combination of properties and cannot replace ECT2/3/4 function in arabidopsis, perhaps suggesting different molecular activities of YTHDF proteins between major taxa.This work was supported by the Novo Nordisk Foundation through a Hallas-Møller Ascending Investigator 2019 grant (NNF19OC0054973) to P.B. and a grant to K.L.-L. via the PRISM (Protein Interactions and Stability in Medicine and Genomics) center (NNF18OC0033950), by the European Molecular Biology Organisation through a long-term fellowship (ALTF 810-2022) to S.v.B., by the European Research Council through a Consolidator grant (ERC-2016-CoG 726417 PATHORISC) to P. B., and by the Independent Research Fund Denmark through a Research Project2 grant (9040-00409B)Peer reviewedPublic Library of ScienceNovo Nordisk FoundationEMBOEuropean Research CouncilIndependent Research Fund DenmarkConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/378900https://api.elsevier.com/content/abstract/scopus_id/85174361857reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#NNF19OC0054973NNF18OC0033950ALTF 810-2022ERC-2016-CoG 726417 PATHORISC9040-00409BPLoS geneticshttps://doi.org/10.1371/journal.pgen.1010980Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3789002026-05-22T06:33:51Z
dc.title.none.fl_str_mv Insights into the conservation and diversification of the molecular functions of YTHDF proteins
title Insights into the conservation and diversification of the molecular functions of YTHDF proteins
spellingShingle Insights into the conservation and diversification of the molecular functions of YTHDF proteins
Flores-Téllez, Daniel
YTHDF proteins
Insights
molecular functions
diversification
title_short Insights into the conservation and diversification of the molecular functions of YTHDF proteins
title_full Insights into the conservation and diversification of the molecular functions of YTHDF proteins
title_fullStr Insights into the conservation and diversification of the molecular functions of YTHDF proteins
title_full_unstemmed Insights into the conservation and diversification of the molecular functions of YTHDF proteins
title_sort Insights into the conservation and diversification of the molecular functions of YTHDF proteins
dc.creator.none.fl_str_mv Flores-Téllez, Daniel
Tankmar, Mathias Due
von Bülow, Sören
Chen, Junyu
Lindorff-Larsen, Kresten
Brodersen, Peter
Arribas-Hernández, Laura
author Flores-Téllez, Daniel
author_facet Flores-Téllez, Daniel
Tankmar, Mathias Due
von Bülow, Sören
Chen, Junyu
Lindorff-Larsen, Kresten
Brodersen, Peter
Arribas-Hernández, Laura
author_role author
author2 Tankmar, Mathias Due
von Bülow, Sören
Chen, Junyu
Lindorff-Larsen, Kresten
Brodersen, Peter
Arribas-Hernández, Laura
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Novo Nordisk Foundation
EMBO
European Research Council
Independent Research Fund Denmark
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv YTHDF proteins
Insights
molecular functions
diversification
topic YTHDF proteins
Insights
molecular functions
diversification
description YT521-B homology (YTH) domain proteins act as readers of N6-methyladenosine (m6A) in mRNA. Members of the YTHDF clade determine properties of m6A-containing mRNAs in the cytoplasm. Vertebrates encode three YTHDF proteins whose possible functional specialization is debated. In land plants, the YTHDF clade has expanded from one member in basal lineages to eleven so-called EVOLUTIONARILY CONSERVED C-TERMINAL REGION1-11 (ECT1-11) proteins in Arabidopsis thaliana, named after the conserved YTH domain placed behind a long N-terminal intrinsically disordered region (IDR). ECT2, ECT3 and ECT4 show genetic redundancy in stimulation of primed stem cell division, but the origin and implications of YTHDF expansion in higher plants are unknown, as it is unclear whether it involves acquisition of fundamentally different molecular properties, in particular of their divergent IDRs. Here, we use functional complementation of ect2/ect3/ect4 mutants to test whether different YTHDF proteins can perform the same function when similarly expressed in leaf primordia. We show that stimulation of primordial cell division relies on an ancestral molecular function of the m6A-YTHDF axis in land plants that is present in bryophytes and is conserved over YTHDF diversification, as it appears in all major clades of YTHDF proteins in flowering plants. Importantly, although our results indicate that the YTH domains of all arabidopsis ECT proteins have m6A-binding capacity, lineage-specific neo-functionalization of ECT1, ECT9 and ECT11 happened after late duplication events, and involves altered properties of both the YTH domains, and, especially, of the IDRs. We also identify two biophysical properties recurrent in IDRs of YTHDF proteins able to complement ect2 ect3 ect4 mutants, a clear phase separation propensity and a charge distribution that creates electric dipoles. Human and fly YTHDFs do not have IDRs with this combination of properties and cannot replace ECT2/3/4 function in arabidopsis, perhaps suggesting different molecular activities of YTHDF proteins between major taxa.
publishDate 2023
dc.date.none.fl_str_mv 2023
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/378900
https://api.elsevier.com/content/abstract/scopus_id/85174361857
url http://hdl.handle.net/10261/378900
https://api.elsevier.com/content/abstract/scopus_id/85174361857
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
NNF19OC0054973
NNF18OC0033950
ALTF 810-2022
ERC-2016-CoG 726417 PATHORISC
9040-00409B
PLoS genetics
https://doi.org/10.1371/journal.pgen.1010980
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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