Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation

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  • dc.contributor.author Di Vona, Chiara, 1981-
  • dc.contributor.author Barba Moreno, Laura, 1989-
  • dc.contributor.author Ferrari, Roberto
  • dc.contributor.author Luna, Susana de la
  • dc.date.accessioned 2024-02-13T07:18:58Z
  • dc.date.available 2024-02-13T07:18:58Z
  • dc.date.issued 2023
  • dc.description.abstract Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated to ensure the appropriate assembly of ribosomes and to respond to the growth demands of cells. The elements regulating the transcription of RP genes (RPGs) have been characterized in yeast and Drosophila, yet how cells regulate the production of RPs in mammals is less well understood. Here, we show that a subset of RPG promoters is characterized by the presence of the palindromic TCTCGCGAGA motif and marked by the recruitment of the protein kinase DYRK1A. The presence of DYRK1A at these promoters is associated with the enhanced binding of the TATA-binding protein, TBP, and it is negatively correlated with the binding of the GABP transcription factor, establishing at least two clusters of RPGs that could be coordinately regulated. However, DYRK1A silencing leads to a global reduction in RPGs mRNAs, pointing at DYRK1A activities beyond those dependent on its chromatin association. Significantly, cells in which DYRK1A is depleted have reduced RP levels, fewer ribosomes, reduced global protein synthesis and a smaller size. We therefore propose a novel role for DYRK1A in coordinating the expression of genes encoding RPs, thereby controlling cell growth in mammals.
  • dc.description.sponsorship This research was supported by the Spanish Ministry of Science and Innovation (BFU2016-76141-P, PID2019-107185GB-I00, AEI/FEDER) and Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya (grant number 2021SGR01229) to S.d.l.L. and the Departments of Excellence’ program of the Italian Ministry for University and Research (MIUR, 2018-2022 and MUR, 2023-2027) to R.F. L.B. was a FPU predoctoral fellow (FPU13/02400). We acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033) and the Generalitat de Catalunya through the CERCA program. We are grateful to the CRG/UPF Proteomics Unit, which is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) and a member of the PRB3-ProteoRed (PT17/0019, Instituto de Salud Carlos III and ERDF).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Di Vona C, Barba L, Ferrari R, de la Luna S. Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation. Biomolecules. 2023 Dec 25;14(1):31. DOI: 10.3390/biom14010031
  • dc.identifier.doi http://dx.doi.org/10.3390/biom14010031
  • dc.identifier.issn 2218-273X
  • dc.identifier.uri http://hdl.handle.net/10230/59087
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Biomolecules. 2023 Dec 25;14(1):31
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-76141-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-107185GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
  • dc.rights © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword DYRK1A
  • dc.subject.keyword TCTCGCGAGA
  • dc.subject.keyword Ribosomal proteins
  • dc.subject.keyword Transcription
  • dc.subject.keyword Translation
  • dc.title Loss of the DYRK1A Protein Kinase Results in the Reduction in Ribosomal Protein Gene Expression, Ribosome Mass and Reduced Translation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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