MicroRNAs (miRNAs) are small noncoding RNAs that can play critical roles in regulating various cellular processes, including during many parasitic infections. Here, we report a regulatory role for miR-34c-3p in cAMP-independent regulation of host cell protein kinase A (PKA) activity in Theileria annulata-infected bovine leukocytes. We identified prkar2b (cAMP-dependent protein kinase A type II-beta regulatory subunit) as a novel miR-34c-3p target gene and demonstrate how infection-induced upregulation of miR-34c-3p repressed PRKAR2B expression to increase PKA activity. As a result, the disseminating tumorlike phenotype of T. annulata-transformed macrophages is enhanced. Finally, we extend our observations to Plasmodium falciparum-parasitized red blood cells, where infection-induced augmentation in miR-34c-3p levels led to a drop in the amount of prkar2b mRNA and increased PKA activity. Collectively, our findings represent a novel cAMP-independent way of regulating host cell PKA activity in infections by Theileria and Plasmodium parasites.
|Original language||English (US)|
|State||Published - Feb 27 2023|
Bibliographical noteKAUST Repository Item: Exported on 2023-03-02
Acknowledged KAUST grant number(s): BAS/1/1020-01-01, OSR-2015-CRG4-2610
Acknowledgements: This study was supported by a Competitive Research Grant (CRG) from the Office for Sponsored Research (OSR-2015-CRG4-2610) at King Abdullah University of Science and Technology (KAUST), awarded to A.P. and G.L., M.H., F.B.-R., and Z.R. acknowledge KAUST for postdoctoral fellowships. S.M. and T.M. were supported by AP baseline funding (BAS/1/1020-01-01) from KAUST. G.L. also acknowledges ANR-11-LABX-0024 and core support from INSERM and the CNRS. FACS was performed with the help of the Cytometry and Immunobiology Facility (CYBIO) of the Cochin Institute (INSERM U1016).