Cyclic oligoadenylate signalling mediates Mycobacterium tuberculosis CRISPR defence
| Autor: | Tess Hoogeboom, Januka S Athukoralage, Sabine Grüschow, Malcolm F. White, Shirley Graham |
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| Přispěvatelé: | The Royal Society, BBSRC, University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex |
| Rok vydání: | 2019 |
| Předmět: |
System
RM QH301 Biology CRISPR-Associated Proteins NDAS Adaptive Immunity Biology Degradation QH301 03 medical and health sciences SDG 3 - Good Health and Well-being Genetics CRISPR Clustered Regularly Interspaced Short Palindromic Repeats QR180 Immunology Ribonuclease 030304 developmental biology RNA Cleavage DNA cleavage 0303 health sciences CRISPR interference Oligoribonucleotides CSX1 Adenine Nucleotides Nucleic Acid Enzymes Oligonucleotide Effector Protein 030302 biochemistry & molecular biology Immunity RNA Mycobacterium tuberculosis Acquired immune system RM Therapeutics. Pharmacology 3. Good health Cell biology Interspersed Repetitive Sequences Prokaryotic Cells Crystal-structure CMS complex QR180 biology.protein CRISPR-Cas Systems HD domain Signal Transduction |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Royal Society Challenge Grant [REF: CH160014 to M.F.W.]; Biotechnology and Biological Sciences Research Council [REF: BB/S000313/1 to M.F.W.]. Funding for open access charge: Institutional Block Grant. The CRISPR system provides adaptive immunity against mobile genetic elements (MGE) in prokaryotes. In type III CRISPR systems, an effector complex programmed by CRISPR RNA detects invading RNA, triggering a multi-layered defence that includes target RNA cleavage, licencing of an HD DNA nuclease domain and synthesis of cyclic oligoadenylate (cOA) molecules. cOA activates the Csx1/Csm6 family of effectors, which degrade RNA non-specifically to enhance immunity. Type III systems are found in diverse archaea and bacteria, including the human pathogen Mycobacterium tuberculosis. Here, we report a comprehensive analysis of the in vitro and in vivo activities of the type III-A M. tuberculosis CRISPR system. We demonstrate that immunity against MGE may be achieved predominantly via a cyclic hexa-adenylate (cA6) signalling pathway and the ribonuclease Csm6, rather than through DNA cleavage by the HD domain. Furthermore, we show for the first time that a type III CRISPR system can be reprogrammed by replacing the effector protein, which may be relevant for maintenance of immunity in response to pressure from viral anti-CRISPRs. These observations demonstrate that M. tuberculosis has a fully-functioning CRISPR interference system that generates a range of cyclic and linear oligonucleotides of known and unknown functions, potentiating fundamental and applied studies. Publisher PDF |
| Databáze: | OpenAIRE |
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