Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress

T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein (RBP) that plays a multifunctional role in RNA metabolism. TIA1 has three RNA-Recognition Motifs (RRMs) and a prion-like carboxyl C-terminal domain (LCD) with intrinsically disordered regions (IDR) implicated in the dynamics (i.e., form...

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Autores: Alcalde-Rey, Isabel, Ramos Velasco, Beatriz, Alcalde, José, Izquierdo, José M.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/373645
Acceso en línea:http://hdl.handle.net/10261/373645
Access Level:acceso abierto
Palabra clave:TIA1
TIAR
Stress granules
Welander distal myopathy
Oxidative stress
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spelling Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative StressAlcalde-Rey, IsabelRamos Velasco, BeatrizAlcalde, JoséIzquierdo, José M.TIA1TIARStress granulesWelander distal myopathyOxidative stressT-cell intracellular antigen 1 (TIA1) is an RNA-binding protein (RBP) that plays a multifunctional role in RNA metabolism. TIA1 has three RNA-Recognition Motifs (RRMs) and a prion-like carboxyl C-terminal domain (LCD) with intrinsically disordered regions (IDR) implicated in the dynamics (i.e., formation, assembly, and disassembly) of transient RNA-protein aggregates known as stress granules (SGs). A protein related to TIA1 is its paralog TIA1-related/like protein (TIAR/TIAL1), whose amino acid sequence, structural organisation, and molecular and cellular functions are highly conserved with TIA1. Both proteins are the main components of SGs, which are non-membranous RNA-protein condensates formed under stress to promote cell survival. Welander distal myopathy (WDM) is a late-onset muscular dystrophy that has been linked to a single-nucleotide substitution (c.1362G>A; p.E384K) in the gene encoding the TIA1 protein, which impacts TIA1-dependent SGs dynamics. Herein, we have analysed cellular and molecular aspects by targeting mutagenesis to position 384 to understand its molecular grammar in an amino acid/proteinogenic-dependent or -independent manner under oxidative stress. The observations suggest differential, even opposing, behaviours between TIA1 and TIAR in the presence of specific amino acids with negative and positive charges, and also uncharged acids, at equivalent positions of TIA1 and TIAR, respectively. Collectively, these findings illustrate a characteristic molecular grammar of TIAR- and TIA1-dependent SGs under oxidative conditions, suggesting a gain of versatility between two structurally and functionally highly conserved/related proteins.Research in our laboratory is supported by the Ministerio de Ciencia, Innovación y Universidades and Agencia Española de Investigación through FEDER funds (PID2021-126152OB-I00) (MICIU/AEI/FEDER, UE). The CBMSO receives an institutional grant from the Fundación Ramón Areces and Banco de Santander.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionFundación Ramón ArecesBanco SantanderConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501application/pdfhttp://hdl.handle.net/10261/373645reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/cells13231961https://doi.org/10.3390/cells13231961Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3736452026-05-22T06:33:51Z
dc.title.none.fl_str_mv Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
title Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
spellingShingle Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
Alcalde-Rey, Isabel
TIA1
TIAR
Stress granules
Welander distal myopathy
Oxidative stress
title_short Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
title_full Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
title_fullStr Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
title_full_unstemmed Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
title_sort Decoding the Molecular Grammar of TIA1-Dependent Stress Granules in Proteostasis and Welander Distal Myopathy Under Oxidative Stress
dc.creator.none.fl_str_mv Alcalde-Rey, Isabel
Ramos Velasco, Beatriz
Alcalde, José
Izquierdo, José M.
author Alcalde-Rey, Isabel
author_facet Alcalde-Rey, Isabel
Ramos Velasco, Beatriz
Alcalde, José
Izquierdo, José M.
author_role author
author2 Ramos Velasco, Beatriz
Alcalde, José
Izquierdo, José M.
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Fundación Ramón Areces
Banco Santander
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv TIA1
TIAR
Stress granules
Welander distal myopathy
Oxidative stress
topic TIA1
TIAR
Stress granules
Welander distal myopathy
Oxidative stress
description T-cell intracellular antigen 1 (TIA1) is an RNA-binding protein (RBP) that plays a multifunctional role in RNA metabolism. TIA1 has three RNA-Recognition Motifs (RRMs) and a prion-like carboxyl C-terminal domain (LCD) with intrinsically disordered regions (IDR) implicated in the dynamics (i.e., formation, assembly, and disassembly) of transient RNA-protein aggregates known as stress granules (SGs). A protein related to TIA1 is its paralog TIA1-related/like protein (TIAR/TIAL1), whose amino acid sequence, structural organisation, and molecular and cellular functions are highly conserved with TIA1. Both proteins are the main components of SGs, which are non-membranous RNA-protein condensates formed under stress to promote cell survival. Welander distal myopathy (WDM) is a late-onset muscular dystrophy that has been linked to a single-nucleotide substitution (c.1362G>A; p.E384K) in the gene encoding the TIA1 protein, which impacts TIA1-dependent SGs dynamics. Herein, we have analysed cellular and molecular aspects by targeting mutagenesis to position 384 to understand its molecular grammar in an amino acid/proteinogenic-dependent or -independent manner under oxidative stress. The observations suggest differential, even opposing, behaviours between TIA1 and TIAR in the presence of specific amino acids with negative and positive charges, and also uncharged acids, at equivalent positions of TIA1 and TIAR, respectively. Collectively, these findings illustrate a characteristic molecular grammar of TIAR- and TIA1-dependent SGs under oxidative conditions, suggesting a gain of versatility between two structurally and functionally highly conserved/related proteins.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/373645
url http://hdl.handle.net/10261/373645
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-126152OB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/cells13231961
https://doi.org/10.3390/cells13231961
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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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