Mark A. Katz, Edith M. Sawyer, Luke Oriolt, Albina Kozlova, Madison C. Williams, Shally R. Margolis, Matthew Johnson, Joseph Bondy-Denomy, Alexander J. Meeske
{"title":"多种病毒 cas 基因拮抗 CRISPR 免疫力","authors":"Mark A. Katz, Edith M. Sawyer, Luke Oriolt, Albina Kozlova, Madison C. Williams, Shally R. Margolis, Matthew Johnson, Joseph Bondy-Denomy, Alexander J. Meeske","doi":"10.1038/s41586-024-07923-x","DOIUrl":null,"url":null,"abstract":"<p>Prokaryotic CRISPR–Cas immunity is subverted by anti-CRISPRs (Acrs), which inhibit Cas protein activities when expressed during the phage lytic cycle or from resident prophages or plasmids<sup>1</sup>. Acrs often bind to specific cognate Cas proteins, and hence inhibition is typically limited to a single CRISPR–Cas subtype<sup>2</sup>. Furthermore, although acr genes are frequently organized together in phage-associated gene clusters<sup>3</sup>, how such inhibitors initially evolve has remained unclear. Here we investigated the Acr content and inhibition specificity of diverse <i>Listeria</i> isolates, which naturally harbour four CRISPR–Cas systems (types I-B, II-A, II-C and VI-A). We observed widespread antagonism of CRISPR, which we traced to 11 previously unknown and 4 known acr gene families encoded by endogenous mobile elements. Among these were two Acrs that possess sequence homology to type I-B Cas proteins, one of which assembles into a defective interference complex. Surprisingly, an additional type I-B Cas homologue did not affect type I immunity, but instead inhibited the RNA-targeting type VI CRISPR system by means of CRISPR RNA (crRNA) degradation. By probing viral sequence databases, we detected abundant orphan cas genes located within putative anti-defence gene clusters. Among them, we verified the activity of a particularly broad-spectrum <i>cas3</i> homologue that inhibits type I-B, II-A and VI-A CRISPR immunity. Our observations provide direct evidence of Acr evolution by cas gene co-option, and new genes with potential for broad-spectrum control of genome editing technologies.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":null,"pages":null},"PeriodicalIF":50.5000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diverse viral cas genes antagonize CRISPR immunity\",\"authors\":\"Mark A. Katz, Edith M. Sawyer, Luke Oriolt, Albina Kozlova, Madison C. Williams, Shally R. Margolis, Matthew Johnson, Joseph Bondy-Denomy, Alexander J. Meeske\",\"doi\":\"10.1038/s41586-024-07923-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Prokaryotic CRISPR–Cas immunity is subverted by anti-CRISPRs (Acrs), which inhibit Cas protein activities when expressed during the phage lytic cycle or from resident prophages or plasmids<sup>1</sup>. Acrs often bind to specific cognate Cas proteins, and hence inhibition is typically limited to a single CRISPR–Cas subtype<sup>2</sup>. Furthermore, although acr genes are frequently organized together in phage-associated gene clusters<sup>3</sup>, how such inhibitors initially evolve has remained unclear. Here we investigated the Acr content and inhibition specificity of diverse <i>Listeria</i> isolates, which naturally harbour four CRISPR–Cas systems (types I-B, II-A, II-C and VI-A). We observed widespread antagonism of CRISPR, which we traced to 11 previously unknown and 4 known acr gene families encoded by endogenous mobile elements. Among these were two Acrs that possess sequence homology to type I-B Cas proteins, one of which assembles into a defective interference complex. Surprisingly, an additional type I-B Cas homologue did not affect type I immunity, but instead inhibited the RNA-targeting type VI CRISPR system by means of CRISPR RNA (crRNA) degradation. By probing viral sequence databases, we detected abundant orphan cas genes located within putative anti-defence gene clusters. Among them, we verified the activity of a particularly broad-spectrum <i>cas3</i> homologue that inhibits type I-B, II-A and VI-A CRISPR immunity. Our observations provide direct evidence of Acr evolution by cas gene co-option, and new genes with potential for broad-spectrum control of genome editing technologies.</p>\",\"PeriodicalId\":18787,\"journal\":{\"name\":\"Nature\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":50.5000,\"publicationDate\":\"2024-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41586-024-07923-x\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41586-024-07923-x","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Diverse viral cas genes antagonize CRISPR immunity
Prokaryotic CRISPR–Cas immunity is subverted by anti-CRISPRs (Acrs), which inhibit Cas protein activities when expressed during the phage lytic cycle or from resident prophages or plasmids1. Acrs often bind to specific cognate Cas proteins, and hence inhibition is typically limited to a single CRISPR–Cas subtype2. Furthermore, although acr genes are frequently organized together in phage-associated gene clusters3, how such inhibitors initially evolve has remained unclear. Here we investigated the Acr content and inhibition specificity of diverse Listeria isolates, which naturally harbour four CRISPR–Cas systems (types I-B, II-A, II-C and VI-A). We observed widespread antagonism of CRISPR, which we traced to 11 previously unknown and 4 known acr gene families encoded by endogenous mobile elements. Among these were two Acrs that possess sequence homology to type I-B Cas proteins, one of which assembles into a defective interference complex. Surprisingly, an additional type I-B Cas homologue did not affect type I immunity, but instead inhibited the RNA-targeting type VI CRISPR system by means of CRISPR RNA (crRNA) degradation. By probing viral sequence databases, we detected abundant orphan cas genes located within putative anti-defence gene clusters. Among them, we verified the activity of a particularly broad-spectrum cas3 homologue that inhibits type I-B, II-A and VI-A CRISPR immunity. Our observations provide direct evidence of Acr evolution by cas gene co-option, and new genes with potential for broad-spectrum control of genome editing technologies.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.