miR-34c-3p Regulates Protein Kinase A Activity Independent of cAMP by Dicing prkar2b Transcripts in Theileria annulata-Infected Leukocytes

Abstract
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.

Citation
Haidar, M., Tajeri, S., Momeux, L., Mourier, T., Ben-Rached, F., Mfarrej, S., Rchiad, Z., Pain, A., & Langsley, G. (2023). miR-34c-3p Regulates Protein Kinase A Activity Independent of cAMP by Dicing prkar2b Transcripts in Theileria annulata-Infected Leukocytes. MSphere. https://doi.org/10.1128/msphere.00526-22

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).

Publisher
American Society for Microbiology

Journal
mSphere

DOI
10.1128/msphere.00526-22

PubMed ID
36847534

Additional Links
https://journals.asm.org/doi/10.1128/msphere.00526-22

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