Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay

The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nucle...

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Autores: Pérez Ortín, José E., Jordán Pla, Antonio, Zang, Yujie, Moreno García, Jorge, Bassot, Claudio, Barba Aliaga, Marina, Campos Mata, Leire de, 1991-, Choder, Mordechai, Díez Antón, Juana, 1962-, Piazza, Ilaria, Pelechano, Vicent, García Martínez, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/60779
Acceso en línea:http://hdl.handle.net/10230/60779
http://dx.doi.org/10.1002/yea.3968
Access Level:acceso abierto
Palabra clave:C‐terminal domain
Frame Protection Index (FPI)
Saccharomyces cerevisiae
Exoribonuclease
mRNA decay
Synthesis rate
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oai_identifier_str oai:repositori.upf.edu:10230/60779
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
title Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
spellingShingle Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
Pérez Ortín, José E.
C‐terminal domain
Frame Protection Index (FPI)
Saccharomyces cerevisiae
Exoribonuclease
mRNA decay
Synthesis rate
title_short Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
title_full Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
title_fullStr Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
title_full_unstemmed Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
title_sort Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
dc.creator.none.fl_str_mv Pérez Ortín, José E.
Jordán Pla, Antonio
Zang, Yujie
Moreno García, Jorge
Bassot, Claudio
Barba Aliaga, Marina
Campos Mata, Leire de, 1991-
Choder, Mordechai
Díez Antón, Juana, 1962-
Piazza, Ilaria
Pelechano, Vicent
García Martínez, José
author Pérez Ortín, José E.
author_facet Pérez Ortín, José E.
Jordán Pla, Antonio
Zang, Yujie
Moreno García, Jorge
Bassot, Claudio
Barba Aliaga, Marina
Campos Mata, Leire de, 1991-
Choder, Mordechai
Díez Antón, Juana, 1962-
Piazza, Ilaria
Pelechano, Vicent
García Martínez, José
author_role author
author2 Jordán Pla, Antonio
Zang, Yujie
Moreno García, Jorge
Bassot, Claudio
Barba Aliaga, Marina
Campos Mata, Leire de, 1991-
Choder, Mordechai
Díez Antón, Juana, 1962-
Piazza, Ilaria
Pelechano, Vicent
García Martínez, José
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C‐terminal domain
Frame Protection Index (FPI)
Saccharomyces cerevisiae
Exoribonuclease
mRNA decay
Synthesis rate
topic C‐terminal domain
Frame Protection Index (FPI)
Saccharomyces cerevisiae
Exoribonuclease
mRNA decay
Synthesis rate
description The yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' → 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/60779
http://dx.doi.org/10.1002/yea.3968
url http://hdl.handle.net/10230/60779
http://dx.doi.org/10.1002/yea.3968
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Yeast. 2024 Jun 14
info:eu-repo/grantAgreement/EC/H2020/948544
info:eu-repo/grantAgreement/ES/2PE/PID2020-112853GB-C31
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decayPérez Ortín, José E.Jordán Pla, AntonioZang, YujieMoreno García, JorgeBassot, ClaudioBarba Aliaga, MarinaCampos Mata, Leire de, 1991-Choder, MordechaiDíez Antón, Juana, 1962-Piazza, IlariaPelechano, VicentGarcía Martínez, JoséC‐terminal domainFrame Protection Index (FPI)Saccharomyces cerevisiaeExoribonucleasemRNA decaySynthesis rateThe yeast Saccharomyces cerevisiae and most eukaryotes carry two 5' → 3' exoribonuclease paralogs. In yeast, they are called Xrn1, which shuttles between the nucleus and the cytoplasm, and executes major cytoplasmic messenger RNA (mRNA) decay, and Rat1, which carries a strong nuclear localization sequence (NLS) and localizes to the nucleus. Xrn1 is 30% identical to Rat1 but has an extra ~500 amino acids C-terminal extension. In the cytoplasm, Xrn1 can degrade decapped mRNAs during the last round of translation by ribosomes, a process referred to as "cotranslational mRNA decay." The division of labor between the two enzymes is still enigmatic and serves as a paradigm for the subfunctionalization of many other paralogs. Here we show that Rat1 is capable of functioning in cytoplasmic mRNA decay, provided that Rat1 remains cytoplasmic due to its NLS disruption (cRat1). This indicates that the physical segregation of the two paralogs plays roles in their specific functions. However, reversing segregation is not sufficient to fully complement the Xrn1 function. Specifically, cRat1 can partially restore the cell volume, mRNA stability, the proliferation rate, and 5' → 3' decay alterations that characterize xrn1Δ cells. Nevertheless, cotranslational decay is only slightly complemented by cRat1. The use of the AlphaFold prediction for cRat1 and its subsequent docking with the ribosome complex and the sequence conservation between cRat1 and Xrn1 suggest that the tight interaction with the ribosome observed for Xrn1 is not maintained in cRat1. Adding the Xrn1 C-terminal domain to Rat1 does not improve phenotypes, which indicates that lack of the C-terminal is not responsible for partial complementation. Overall, during evolution, it appears that the two paralogs have acquired specific characteristics to make functional partitioning beneficial.We acknowledge A. Johnson for the gift of the Xrn1 antibody. This work was funded with grants from: the Spanish MCIN/AEI/10.13039/501100011033 [PID2020-112853GB-C31] to José E. Pérez-Ortín; the Swedish Foundation's Starting Grant (Ragnar Söderberg Foundation); the Swedish Research Council [VR 2020-01480, 2021-06112, and 2019-02335]; a Wallenberg Academy Fellowship [2021.0167]; Vinnova (2020-03620), the Karolinska Institutet (SciLifeLab Fellowship, SFO and KI funds) to Vicent Pelechano and the Israel Science Foundation (ISF) 301/20 for Mordechai Choder. Yujie Zhang is funded by a fellowship from the China Scholarship Council. Ilaria Piazza receives funding from the Helmholtz Young Investigators program of the Helmholtz Association and from the European Research Council (ERC) in the European Union's Horizon 2020 Research and Innovation Programme (grant agreement ERC-STG No 948544). The computational analysis was partially performed with the resources provided by the Swedish National Infrastructure for Computing (SNIC) through the Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX), partially funded by the Swedish Research Council with grant agreement number 2018-05973.Wiley202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/60779http://dx.doi.org/10.1002/yea.3968reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésYeast. 2024 Jun 14info:eu-repo/grantAgreement/EC/H2020/948544info:eu-repo/grantAgreement/ES/2PE/PID2020-112853GB-C31© 2024 The Author(s). Yeast published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/607792026-06-12T07:21:37Z
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