» Articles » PMID: 26853474

Degradation of Phage Transcripts by CRISPR-Associated RNases Enables Type III CRISPR-Cas Immunity

Overview
Journal Cell
Publisher Cell Press
Specialty Cell Biology
Date 2016 Feb 9
PMID 26853474
Citations 115
Authors
Affiliations
Soon will be listed here.
Abstract

Type III-A CRISPR-Cas systems defend prokaryotes against viral infection using CRISPR RNA (crRNA)-guided nucleases that perform co-transcriptional cleavage of the viral target DNA and its transcripts. Whereas DNA cleavage is essential for immunity, the function of RNA targeting is unknown. Here, we show that transcription-dependent targeting results in a sharp increase of viral genomes in the host cell when the target is located in a late-expressed phage gene. In this targeting condition, mutations in the active sites of the type III-A RNases Csm3 and Csm6 lead to the accumulation of the target phage mRNA and abrogate immunity. Csm6 is also required to provide defense in the presence of mutated phage targets, when DNA cleavage efficiency is reduced. Our results show that the degradation of phage transcripts by CRISPR-associated RNases ensures robust immunity in situations that lead to a slow clearance of the target DNA.

Citing Articles

Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes.

Jungfer K, Moravcik S, Garcia-Doval C, Knorlein A, Hall J, Jinek M Nucleic Acids Res. 2025; 53(2).

PMID: 39817514 PMC: 11734703. DOI: 10.1093/nar/gkae1277.


Engineering Phages to Fight Multidrug-Resistant Bacteria.

Peng H, Chen I, Qimron U Chem Rev. 2024; 125(2):933-971.

PMID: 39680919 PMC: 11758799. DOI: 10.1021/acs.chemrev.4c00681.


CRISPR-based gene editing technology and its application in microbial engineering.

Wei J, Li Y Eng Microbiol. 2024; 3(4):100101.

PMID: 39628916 PMC: 11610974. DOI: 10.1016/j.engmic.2023.100101.


Cas10 relieves host growth arrest to facilitate spacer retention during type III-A CRISPR-Cas immunity.

Aviram N, Shilton A, Lyn N, Reis B, Brivanlou A, Marraffini L Cell Host Microbe. 2024; 32(12):2050-2062.e6.

PMID: 39626678 PMC: 11708336. DOI: 10.1016/j.chom.2024.11.005.


Engineered transcription-associated Cas9 targeting in eukaryotic cells.

Goldberg G, Kogenaru M, Keegan S, Haase M, Kagermazova L, Arias M Nat Commun. 2024; 15(1):10287.

PMID: 39604381 PMC: 11603292. DOI: 10.1038/s41467-024-54629-9.


References
1.
Hale C, Cocozaki A, Li H, Terns R, Terns M . Target RNA capture and cleavage by the Cmr type III-B CRISPR-Cas effector complex. Genes Dev. 2014; 28(21):2432-43. PMC: 4215187. DOI: 10.1101/gad.250712.114. View

2.
Weinberger A, Wolf Y, Lobkovsky A, Gilmore M, Koonin E . Viral diversity threshold for adaptive immunity in prokaryotes. mBio. 2012; 3(6):e00456-12. PMC: 3517865. DOI: 10.1128/mBio.00456-12. View

3.
Tamulaitis G, Kazlauskiene M, Manakova E, Venclovas C, Nwokeoji A, Dickman M . Programmable RNA shredding by the type III-A CRISPR-Cas system of Streptococcus thermophilus. Mol Cell. 2014; 56(4):506-17. DOI: 10.1016/j.molcel.2014.09.027. View

4.
Ramia N, Spilman M, Tang L, Shao Y, Elmore J, Hale C . Essential structural and functional roles of the Cmr4 subunit in RNA cleavage by the Cmr CRISPR-Cas complex. Cell Rep. 2014; 9(5):1610-1617. PMC: 4269474. DOI: 10.1016/j.celrep.2014.11.007. View

5.
Peng W, Feng M, Feng X, Liang Y, She Q . An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference. Nucleic Acids Res. 2014; 43(1):406-17. PMC: 4288192. DOI: 10.1093/nar/gku1302. View