CRISPR-Cas and prokaryotic Argonaute (pAgo) are nucleic acid (NA)-guided defense systems that protect prokaryotes against the invasion of mobile genetic elements. Previous studies established that they are directed by NA fragments (guides) to recognize invading complementary NA (targets), and that they cleave the targets to silence the invaders. Nevertheless, growing evidence indicates that many CRISPR-Cas and pAgo systems exploit the abortive infection (Abi) strategy to confer immunity. The CRISPR-Cas and pAgo Abi systems typically sense invaders using the NA recognition ability and activate various toxic effectors to kill the infected cells to prevent the invaders from spreading. This review summarizes the diverse mechanisms of these CRISPR-Cas and pAgo systems, and highlights their critical roles in the arms race between microbes and invaders.
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http://dx.doi.org/10.1016/j.tim.2022.11.005 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Joint International Research Laboratory of Metabolic and Developmental Sciences, Yazhou Bay Institute of Deepsea Sci-Tech, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Understanding the integration of transgene DNA (T-DNA) in transgenic crops, animals, and clinical applications is paramount for ensuring the stability and expression of inserted genes, which directly influence desired traits and therapeutic outcomes. Analyzing T-DNA integration patterns is essential for identifying potential unintended effects and evaluating the safety and environmental implications of genetically modified organisms (GMOs). This knowledge is crucial for regulatory compliance and fostering public trust in biotechnology by demonstrating transparency in genetic modifications.
View Article and Find Full Text PDFNat Commun
October 2024
Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Eukaryotic Argonaute proteins (eAgos) utilize short nucleic acid guides to target complementary sequences for RNA silencing, while prokaryotic Agos (pAgos) provide immunity against invading plasmids or bacteriophages. The Sir2-domain associated short pAgo (SPARSA) immune system defends against invaders by depleting NAD and triggering cell death. However, the molecular mechanism underlying SPARSA activation remains unknown.
View Article and Find Full Text PDFJ Mol Biol
October 2024
Institute of Gene Biology, Russian Academy of Sciences, Moscow 119334, Russia. Electronic address:
Argonaute nucleases use small nucleic acid guides to recognize and degrade complementary nucleic acid targets. Most prokaryotic Argonautes (pAgos) recognize DNA targets and may play a role in cell immunity against invader genetic elements. We have recently described two related groups of pAgo nucleases that have distinct specificity for DNA guides and RNA targets (DNA > RNA pAgos).
View Article and Find Full Text PDFAntibiotics (Basel)
June 2024
Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine.
Leptospirosis is a major zoonotic disease caused by pathogenic spirochetes in the genus Leptospira, affecting over a million people annually and causing approximately 60,000 deaths. , a key causative agent, likely possesses defense systems against bacteriophages (leptophages), yet these systems are not well understood. We analyzed 402 genomes of using the DefenseFinder tool to identify and characterize the antiphage defense systems.
View Article and Find Full Text PDFNat Commun
June 2024
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
A short prokaryotic Argonaute (pAgo) TIR-APAZ (SPARTA) defense system, activated by invading DNA to unleash its TIR domain for NAD(P) hydrolysis, was recently identified in bacteria. We report the crystal structure of SPARTA heterodimer in the absence of guide-RNA/target-ssDNA (2.66 Å) and a cryo-EM structure of the SPARTA oligomer (tetramer of heterodimers) bound to guide-RNA/target-ssDNA at nominal 3.
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