The DYRK1A protein kinase regulates ribosome mass and translation rates through transcriptional control of ribosomal protein genes expression

Ribosomal proteins (RPs) are evolutionary conserved proteins that are essential for protein translation. RP expression must be tightly regulated, both 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. The dual-specificity tyrosine-regulated kinase 1A (DYRK1A) is known to participate in cell proliferation and differentiation in mammals, and its dysregulation is associated with disease in humans. Here, we show that DYRK1A marks a specific subset of proximal RPG promoters, which are characterized by the presence of the palindromic TCTCGCGAGA motif. The presence of DYRK1A at these promoters is associated with 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. Indeed, DYRK1A depletion leads to a reduction of both RP mRNA and protein. Significantly, cells in which DYRK1A is depleted have fewer ribosomes, reduced global protein synthesis and they are smaller. Based on these results, we propose a novel role for DYRK1A in coordinating the expression of genes encoding RPs, thereby controlling cell growth in mammals.