Proteomics

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The regulation of ribosomal protein genes expression by the protein kinase DYRK1A contributes to the maintenance of ribosome mass and protein translation


ABSTRACT: Ribosomal protein genes (RPGs) coding sequences are highly conserved along evolution; however, promoter features and the machinery involved in their transcriptional regulation are not. In eukaryotes, the main genomic elements and players involved in RPG transcriptional regulation have been mostly characterized in Saccharomyces cerevisiae. However, given the lack of evolutionary conservation of the yeast factors, studies in higher eukaryotes have focused on searching for differential enrichment of transcription factor-binding motifs within the RPG promoters. Among them, the palindromic motif TCTCGCGAGA, which is currently acknowledged as a ZBTB33/KAISO motif, also matches the genomic sequence bound by the protein kinase DYRK1A. DYRK1A, a member of the human family of DYRK kinases, fulfills many diverse functions by phosphorylating a broad set of proteins involved in different cellular processes. One of such functions is to be a chromatin-associated kinase capable of regulating gene expression. Here, we analyze in-depth the presence of DYRK1A at the promoters of human and mouse RPGs and explore its functional consequences. Our results indicate that DYRK1A is a positive regulator of RPGs’ expression at the transcriptional level, and that this effect could, at least in part, contribute to the global reduction in ribosome amounts and protein synthesis observed when DYRK1A is silenced. Therefore, our results further expand the functional spectrum of the kinase as a contributor to the regulation of cell growth in mammalian cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Eva Borràs  

LAB HEAD: Eduard Sabido

PROVIDER: PXD022966 | Pride | 2024-05-22

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
171108_CDSL.pdResult Other
171108_S_CDSL_01_02_2ug.raw Raw
171108_S_CDSL_02_02_2ug.raw Raw
171108_S_CDSL_03_02_2ug.raw Raw
171108_S_CDSL_04_02_2ug.raw Raw
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Publications

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

Di Vona Chiara C   Barba Laura L   Ferrari Roberto R   de la Luna Susana S  

Biomolecules 20231225 1


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 <i>Drosophila</i>, 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  ...[more]

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