Dual-specific tyrosine-regulated kinase 1A (DYRK1A) has key roles in developmental processes and tissue homeostasis, and its dysregulation has been associated with human pathologies. Although DYRK1A is present in the nucleus and cytoplasm, its role in the nuclear compartment was elusive. Now, Di Vona et al. show that DYRK1A is recruited to the promoters of growth-related genes that are actively transcribed by RNA polymerase II (Pol II). Promoter sequences bound by this kinase are characterized by a conserved palindromic motif. Moreover, DYRK1A interacted with and phosphorylated the Pol II carboxy-terminal domain (CTD) at Ser2 and Ser5, and its depletion decreased the association of Pol II with target promoters. Thus, DYRK1A regulates transcription by phosphorylating the CTD at residues necessary for transcriptional elongation.
References
Di Vona, C. et al. Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase. Mol. Cell http://dx.doi.org/10.1016/j.molcel.2014.12.026 (2015)
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Du Toit, A. DYRK1A targets Pol II. Nat Rev Mol Cell Biol 16, 127 (2015). https://doi.org/10.1038/nrm3961
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DOI: https://doi.org/10.1038/nrm3961