Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers

Niewoehner, Ole; Garcia-Doval, Carmela; Rostøl, Jakob T.; Berk, Christian; Schwede, Frank; Bigler, Laurent; Hall, Jonathan; Marraffini, Luciano A.; Jinek, Martin

doi:10.1038/nature23467

Cited by 419 publications

(532 citation statements)

References 43 publications

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“…Recent studies have revealed an immune mechanism in the Class 1 Type III–A system that parallels the target-activated collateral cleavage by Cas13 (Kazlauskiene et al, 2017; Niewoehner et al, 2017). In this system, the multi-subunit Csm effector complex binds RNA transcripts that match the guide crRNA.…”

Section: Type VI Crispr–cas Systemsmentioning

confidence: 99%

The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit

et al. 2017

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CRISPR–Cas systems defend prokaryotes against bacteriophages and mobile genetic elements and serve as the basis for revolutionary tools for genetic engineering. Class 2 CRISPR–Cas systems use single Cas endonucleases paired with guide RNAs to cleave complementary nucleic acid targets, enabling programmable sequence-specific targeting with minimal machinery. Recent discoveries of previously unidentified CRISPR–Cas systems have uncovered a deep reservoir of potential biotechnological tools beyond the well-characterized Type II Cas9 systems. Here we review the current mechanistic understanding of newly discovered single-protein Cas endonucleases. Comparison of these Cas effectors reveals substantial mechanistic diversity, underscoring the phylogenetic divergence of related CRISPR–Cas systems. This diversity has enabled further expansion of CRISPR–Cas biotechnological toolkits, with wide-ranging applications from genome editing to diagnostic tools based on various Cas endonuclease activities. These advances highlight the exciting prospects for future tools based on the continually expanding set of CRISPR–Cas systems.

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Section: Type VI Crispr–cas Systemsmentioning

confidence: 99%

The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit

et al. 2017

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“…Future interkingdom microbial consortia design can also exploit the CRISPR-Cas systems, a microbial strategy to overcome 'invasions' by phages/viruses. While recent studies utilize CRISPR in monoculture systems (Donohoue et al, 2017), the new discovery of the signalling pathway between Cas and Csm complexes uncovered a future research direction of CRISPR regulation by controlling the signal messengers that activate the RNase activity (Kazlauskiene et al, 2017;Niewoehner et al, 2017). Although the CRISPR evolution and adaptation at the consortia level are still limited (Davison et al, 2016;Burstein et al, 2017), the manipulation of communication signals may be feasible in microbial consortia and further adapted to other biotechnological applications.…”

Section: Interkingdom Consortia Have Enhanced Tolerance Towards Extermentioning

confidence: 99%

Interkingdom microbial consortia mechanisms to guide biotechnological applications

Shu

Merino

Okamoto

et al. 2018

Microbial Biotechnology

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SummaryMicrobial consortia are capable of surviving diverse conditions through the formation of synergistic population‐level structures, such as stromatolites, microbial mats and biofilms. Biotechnological applications are poised to capitalize on these unique interactions. However, current artificial co‐cultures constructed for societal benefits, including biosynthesis, agriculture and bioremediation, face many challenges to perform as well as natural consortia. Interkingdom microbial consortia tend to be more robust and have higher productivity compared with monocultures and intrakingdom consortia, but the control and design of these diverse artificial consortia have received limited attention. Further, feasible research techniques and instrumentation for comprehensive mechanistic insights have only recently been established for interkingdom microbial communities. Here, we review these recent advances in technology and our current understanding of microbial interaction mechanisms involved in sustaining or developing interkingdom consortia for biotechnological applications. Some of the interactions among members from different kingdoms follow similar mechanisms observed for intrakingdom microbial consortia. However, unique interactions in interkingdom consortia, including endosymbiosis or interkingdom‐specific cell–cell interactions, provide improved mitigation to external stresses and inhibitory compounds. Furthermore, antagonistic interactions among interkingdom species can promote fitness, diversification and adaptation, along with the production of beneficial metabolites and enzymes for society. Lastly, we shed light on future research directions to develop study methods at the level of metabolites, genes and meta‐omics. These potential research methods could lead to the control and utilization of highly diverse microbial communities.

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“…To increase the sensitivity of the SHERLOCK system, a two‐step signal amplification protocol was developed using two different CRISPR effectors. Collateral ssRNA degradation by the Type III RNAse effector Csm6 is activated by the production of key second messengers that can be generated by the activity of Cas13. Using two different fluorescent reporters in the same channel with specificity to Csm6 or Cas13a, the sensitivity of SHERLOCK 2 could be further improved reaching nearly single molecule detection …”

Section: Novel Crispr‐based Tools For Cancer Diagnosticsmentioning

confidence: 99%

Cancer diagnosis and immunotherapy in the age of CRISPR

Cook

Ventura

2018

Genes Chromosomes & Cancer

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The explosion in genome editing technologies that has occurred in the past decade has revolutionized cancer research and promises to improve cancer diagnosis and therapy. Ongoing efforts include engineering of chimeric antigen receptor‐T cells using clustered regularly interspaced short palindromic repeats (CRISPR) to generate a safer, more effective therapy with improved performance in immunologically “cold” tumors, as well as clever adaptations of CRISPR enzymes to allow fast, simple, and sensitive detection of specific nucleotide sequences. While still in their infancy, CRISPR‐based cancer therapeutics and diagnostics are developing at an impressive speed and it is likely they will soon impact clinical practice. Here, we summarize their history and the most recent developments.

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Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers

Cited by 419 publications

References 43 publications

The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit

The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit

Interkingdom microbial consortia mechanisms to guide biotechnological applications

Cancer diagnosis and immunotherapy in the age of CRISPR

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