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

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• dc.contributor.author Pérez Ortín, José E.
• dc.contributor.author Jordán Pla, Antonio
• dc.contributor.author Zang, Yujie
• dc.contributor.author Moreno García, Jorge
• dc.contributor.author Bassot, Claudio
• dc.contributor.author Barba Aliaga, Marina
• dc.contributor.author Campos Mata, Leire de, 1991-
• dc.contributor.author Choder, Mordechai
• dc.contributor.author Díez Antón, Juana, 1962-
• dc.contributor.author Piazza, Ilaria
• dc.contributor.author Pelechano, Vicent
• dc.contributor.author García Martínez, José
• dc.date.accessioned 2024-07-18T06:56:34Z
• dc.date.available 2024-07-18T06:56:34Z
• dc.date.issued 2024
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Pérez-Ortín JE, Jordán-Pla A, Zhang Y, Moreno-García J, Bassot C, Barba-Aliaga M, et al. Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay. Yeast. 2024 Jun 14. DOI: 10.1002/yea.3968
• dc.identifier.doi http://dx.doi.org/10.1002/yea.3968
• dc.identifier.issn 0749-503X
• dc.identifier.uri http://hdl.handle.net/10230/60779
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Yeast. 2024 Jun 14
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948544
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-112853GB-C31
• dc.rights © 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword C‐terminal domain
• dc.subject.keyword Frame Protection Index (FPI)
• dc.subject.keyword Saccharomyces cerevisiae
• dc.subject.keyword Exoribonuclease
• dc.subject.keyword mRNA decay
• dc.subject.keyword Synthesis rate
• dc.title Comparison of Xrn1 and Rat1 5' → 3' exoribonucleases in budding yeast supports the specific role of Xrn1 in cotranslational mRNA decay
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion