Discovery of widespread type I and type V CRISPR-Cas inhibitors

被引:191
作者
Marino, Nicole D. [1 ]
Zhang, Jenny Y. [1 ]
Borges, Adair L. [1 ]
Sousa, Alexander A. [2 ,3 ,4 ]
Leon, Lina M. [1 ]
Rauch, Benjamin J. [1 ,7 ]
Walton, Russell T. [2 ,3 ,4 ]
Berry, Joel D. [1 ,8 ]
Joung, J. Keith [2 ,3 ,4 ,5 ]
Kleinstiver, Benjamin P. [2 ,3 ,4 ,5 ]
Bondy-Denomy, Joseph [1 ,6 ]
机构
[1] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[2] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA
[3] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA
[4] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA
[5] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA
[6] Univ Calif San Francisco, Quantitat Biosci Inst, San Francisco, CA 94143 USA
[7] Zymergen, Emeryville, CA 94608 USA
[8] Caribou Biosci, Berkeley, CA 94710 USA
基金
美国国家卫生研究院;
关键词
INFECTIOUS BOVINE KERATOCONJUNCTIVITIS; CPF1; MECHANISMS; PROTEINS; SYSTEM; RNA;
D O I
10.1126/science.aau5174
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs-including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a-when assayed in human cells. The acr genes reported here provide useful biotechnological tools and mark the discovery of acr loci in many bacteria and phages.
引用
收藏
页码:240 / 242
页数:3
相关论文
共 18 条
[1]   Moraxella bovoculi sp nov, isolated from calves with infectious bovine keratoconjunctivitis [J].
Angelos, John A. ;
Spinks, Phillip Q. ;
Ball, Louise M. ;
George, Lisle W. .
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, 2007, 57 :789-795
[2]   Novel Moraxella catarrhalis prophages display hyperconserved non-structural genes despite their genomic diversity [J].
Ariff, Amir ;
Wise, Michael J. ;
Kahler, Charlene M. ;
Tay, Chin Yen ;
Peters, Fanny ;
Perkins, Timothy T. ;
Chang, Barbara J. .
BMC GENOMICS, 2015, 16
[3]   Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system [J].
Bondy-Denomy, Joe ;
Pawluk, April ;
Maxwell, Karen L. ;
Davidson, Alan R. .
NATURE, 2013, 493 (7432) :429-U181
[4]   Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins [J].
Bondy-Denomy, Joseph ;
Garcia, Bianca ;
Strum, Scott ;
Du, Mingjian ;
Rollins, MaryClare F. ;
Hidalgo-Reyes, Yurima ;
Wiedenheft, Blake ;
Maxwell, Karen L. ;
Davidson, Alan R. .
NATURE, 2015, 526 (7571) :136-+
[5]   The Discovery, Mechanisms, and Evolutionary Impact of Anti-CRISPRs [J].
Borges, Adair L. ;
Davidson, Alan R. ;
Bondy-Denomy, Joseph .
ANNUAL REVIEW OF VIROLOGY, VOL 4, 2017, 4 :37-59
[6]   Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with infectious bovine keratoconjunctivitis versus the deep nasopharynx of asymptomatic cattle [J].
Dickey, Aaron M. ;
Loy, John D. ;
Bono, James L. ;
Smith, Timothy P. L. ;
Apley, Mike D. ;
Lubbers, Brian V. ;
DeDonder, Keith D. ;
Capik, Sarah F. ;
Larson, Robert L. ;
White, Brad J. ;
Blom, Jochen ;
Chitko-McKown, Carol G. ;
Clawson, Michael L. .
VETERINARY RESEARCH, 2016, 47
[7]   The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA [J].
Fonfara, Ines ;
Richter, Hagen ;
Bratovic, Majda ;
Le Rhun, Anais ;
Charpentier, Emmanuelle .
NATURE, 2016, 532 (7600) :517-+
[8]   Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells [J].
Kleinstiver, Benjamin P. ;
Tsai, Shengdar Q. ;
Prew, Michelle S. ;
Nguyen, Nhu T. ;
Welch, Moira M. ;
Lopez, Jose M. ;
McCaw, Zachary R. ;
Aryee, Martin J. ;
Joung, J. Keith .
NATURE BIOTECHNOLOGY, 2016, 34 (08) :869-+
[9]   Diversity, classification and evolution of CRISPR-Cas systems [J].
Koonin, Eugene V. ;
Makarova, Kira S. ;
Zhang, Feng .
CURRENT OPINION IN MICROBIOLOGY, 2017, 37 :67-78
[10]   Anti-CRISPR: discovery, mechanism and function [J].
Pawluk, April ;
Davidson, Alan R. ;
Maxwell, Karen L. .
NATURE REVIEWS MICROBIOLOGY, 2018, 16 (01) :12-17