Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 546, Issue -, Pages 155-161Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.01.100
Keywords
Calcium; LadS; RsmA; Pseudomonas aeruginosa; Type I-F CRISPR-Cas system
Categories
Funding
- National Institutes of Health [5R01AI109317-04, 1R01AI138203-01]
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Calcium positively regulates the transcription of CRISPR-Cas system via LadS, while RsmA functions as a post-transcriptional regulator; the modulation of CRISPR-Cas system by calcium depends on LadS and RsmA, highlighting their previously unrecognized role in sensing calcium.
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. (c) 2021 Elsevier Inc. All rights reserved.
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