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Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein

Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA targeting systems identified subtype VI...

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Autores principales: Yan, Winston X., Chong, Shaorong, Zhang, Huaibin, Makarova, Kira S., Koonin, Eugene V., Cheng, David R., Scott, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935466/
https://www.ncbi.nlm.nih.gov/pubmed/29551514
http://dx.doi.org/10.1016/j.molcel.2018.02.028
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author Yan, Winston X.
Chong, Shaorong
Zhang, Huaibin
Makarova, Kira S.
Koonin, Eugene V.
Cheng, David R.
Scott, David A.
author_facet Yan, Winston X.
Chong, Shaorong
Zhang, Huaibin
Makarova, Kira S.
Koonin, Eugene V.
Cheng, David R.
Scott, David A.
author_sort Yan, Winston X.
collection PubMed
description Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA targeting systems identified subtype VI-D, encoding dual HEPN-domain containing Cas13d effectors and putative WYL-domain containing accessory proteins (WYL1 and WYL-b1–5). The median size of Cas13d proteins is 190 to 300 amino acids smaller than that of Cas13a-c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and target as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA-manipulation and detection.
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spelling pubmed-59354662019-04-19 Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein Yan, Winston X. Chong, Shaorong Zhang, Huaibin Makarova, Kira S. Koonin, Eugene V. Cheng, David R. Scott, David A. Mol Cell Article Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA targeting systems identified subtype VI-D, encoding dual HEPN-domain containing Cas13d effectors and putative WYL-domain containing accessory proteins (WYL1 and WYL-b1–5). The median size of Cas13d proteins is 190 to 300 amino acids smaller than that of Cas13a-c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and target as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA-manipulation and detection. 2018-03-15 2018-04-19 /pmc/articles/PMC5935466/ /pubmed/29551514 http://dx.doi.org/10.1016/j.molcel.2018.02.028 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This manuscript version is made available under the CC BY-NC-ND 4.0 license.
spellingShingle Article
Yan, Winston X.
Chong, Shaorong
Zhang, Huaibin
Makarova, Kira S.
Koonin, Eugene V.
Cheng, David R.
Scott, David A.
Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title_full Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title_fullStr Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title_full_unstemmed Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title_short Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL domain-containing accessory protein
title_sort cas13d is a compact rna-targeting type vi crispr effector positively modulated by a wyl domain-containing accessory protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935466/
https://www.ncbi.nlm.nih.gov/pubmed/29551514
http://dx.doi.org/10.1016/j.molcel.2018.02.028
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