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Updated: Nov 17, 2025

Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells
Published on: January 5, 2018
Calcium-responsive kinase LadS modulates type I-F CRISPR-Cas adaptive immunity
Chuan-Min Zhou1, Qun Wu2, Biao Wang3
1Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, P. R. China; Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND, 58203-9037, USA; Wuhan University School of Health Sciences, Wuhan, Hubei Province, 430071, P. R. China.
Abstract:
The CRISPR-Cas systems are recently discovered adaptive immune strategies in bacteria and archaea against foreign genetic elements. Although gene-editing enabled by CRISPR-Cas9 has shown great promise for clinical application, little is known about potential mechanisms of CRISPR-Cas systems for regulating their own gene expression and altering the virulence within bacteria. Here, Gram-negative bacterium Pseudomonas aeruginosa PA14 that contains a Type I-F CRISPR-Cas system was used to study the mechanism endogenous CRISPR-Cas of regulation mechanism. We delineated the role of calcium as a positive regulator of the transcription of cas/csy complex and CRISPR-Cas immunity through the two-component system (TCS) protein kinase LadS. Furthermore, we identified a LadS downstream post-transcriptional regulator, RsmA, which targeted translation region of cas mRNA via A(N)GGA motif. Importantly, calcium-mediated influencing of CRISPR-Cas system was dependent on LadS and RsmA. Altogether, our findings uncover the previously unrecognized role of LadS/RsmA in modulating Type I-F CRISPR-Cas system via sensing calcium.
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