Author(s)

Farag Bleiblo^1,2*, Paul Michael², Chilakamarti V. Ramana³, T. C. Tai², Joseph E. Parrillo⁴, Anand Kumar⁵, Aseem Kumar²

¹Department of Microbiology, Faculty of Science, University of Benghazi, Benghazi, Libya.
²Department of Chemistry and Biochemistry and the Biomolecular Sciences Programme, Laurentian University, Sudbury, Canada.
³Department of Medicine, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, NH, USA.
⁴Division of Cardiovascular Disease and Critical Care Medicine, Cooper University Hospital, Robert Wood Johnson Medical School, Camden, NJ, USA.
⁵Section of Critical Care Medicine, University of Manitoba, Winnipeg, Canada.

Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.

STAT1, STAT2, Apoptosis, Bacterial RNA

Bleiblo, F. , Michael, P. , Ramana, C. , Tai, T. , Parrillo, J. , Kumar, A. and Kumar, A. (2020) STAT1 and STAT2 Null Cells Are Resistant to RNA-Induced Apoptosis Due to Deficiency in Constitutive and Inducible Apoptosis-Regulating Genes. American Journal of Molecular Biology, 10, 165-187. doi: 10.4236/ajmb.2020.103012.