Phosphoproteomics identifies the DYRK1B protein kinase as a regulator of processing bodies

Ashford, A. L.; Ber, S.; Ems, M. S.; Duncan, E.; Balmanno, K.; Reeves, H.; Huntly, R.; Cassidy, M. A.; Johnston, H. E.; Oxley, D.; Nthiga, T. M.; Johansen, T.; Kluge, M.; Jacob, R.; Lauth, M.; Cook, S. J.

doi:10.64898/2026.04.29.721300

bioRxiv · 10.64898/2026.04.29.721300

Phosphoproteomics identifies the DYRK1B protein kinase as a regulator of processing bodies

Ashford, A. L.·Ber, S.·Ems, M. S.·Duncan, E.·Balmanno, K.·Reeves, H.·Huntly, R.·Cassidy, M. A.·Johnston, H. E.·Oxley, D.·Nthiga, T. M.·Johansen, T.·Kluge, M.·Jacob, R.·Lauth, M.·Cook, S. J.

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Abstract

Dual-specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) modulates the cell cycle, cell fate during development, and is deregulated in cancer and metabolic syndrome. However, only a few DYRK1B substrates have been defined, so we undertook a phosphoproteomics screen in cells that exhibit inducible DYRK1B expression. Motif analysis revealed enrichment for proline-directed serine or threonine phosphorylation sites (pSer/pThr-Pro), consistent with the consensus motif of class I DYRKs. Gene ontology analysis revealed enrichment of proteins involved in mRNA binding, mRNA processing and ribonucleoprotein complexes. Several processing body (PB) components, including DCP1A, PATL1(PAT1B), EDC3 and 4E-T, were identified as DYRK1B-inducible phosphoproteins. DYRK1B also co-immunoprecipitated with DCP1A, PAT1B, EDC3, EDC4, DDX6 and XRN1. Super-resolution microscopy demonstrated that DYRK1B co-localised with DCP1A, DCP1B and DDX6 in PBs. Activation of DYRK1B increased PB abundance, whereas inhibition, depletion or knockout of DYRK1B reduced phosphorylation of DCP1A and 4E-T and decreased PB number. Re-expression of wild type, but not kinase-dead, DYRK1B restored PB numbers in knockout cells. These findings reveal novel DYRK1B targets and establish DYRK1B as a regulator of processing body abundance. HighlightsO_LIDYRK1B induces phosphorylation of a cluster of RNA binding and processing body associated proteins. C_LIO_LIDYRK1B localises to PBs and associates with multiple PB components. C_LIO_LIDYRK1B controls P-body abundance in a kinase-dependent manner. C_LI

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Ashford, A. L., Ber, S., Ems, M. S., Duncan, E., Balmanno, K., Reeves, H., Huntly, R., Cassidy, M. A., Johnston, H. E., Oxley, D., Nthiga, T. M., Johansen, T., Kluge, M., Jacob, R., Lauth, M., Cook, S. J.. 2026-05-01. Phosphoproteomics identifies the DYRK1B protein kinase as a regulator of processing bodies. https://doi.org/10.64898/2026.04.29.721300

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