The Cas10 nuclease activity relieves host dormancy to facilitate spacer acquisition and retention during type III-A CRISPR immunity.

Autor:	Aviram N; Laboratory of Bacteriology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA., Shilton AK; Laboratory of Bacteriology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA., Lyn NG; Laboratory of Bacteriology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA., Reis BS; Laboratory of Mucosal Immunology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA., Brivanlou A; Laboratory of Bacteriology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA., Marraffini LA; Laboratory of Bacteriology, the Rockefeller University, 1230 York Ave, New York, NY 10065, USA.; Howard Hughes Medical Institute, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 12. Date of Electronic Publication: 2024 Feb 12.
DOI:	10.1101/2024.02.11.579731
Abstrakt:	A hallmark of CRISPR immunity is the acquisition of short viral DNA sequences, known as spacers, that are transcribed into guide RNAs to recognize complementary sequences. The staphylococcal type III-A CRISPR-Cas system uses guide RNAs to locate viral transcripts and start a response that displays two mechanisms of immunity. When immunity is triggered by an early-expressed phage RNA, degradation of viral ssDNA can cure the host from infection. In contrast, when the RNA guide targets a late-expressed transcript, defense requires the activity of Csm6, a non-specific RNase. Here we show that Csm6 triggers a growth arrest of the host that provides immunity at the population level which hinders viral propagation to allow the replication of non-infected cells. We demonstrate that this mechanism leads to defense against not only the target phage but also other viruses present in the population that fail to replicate in the arrested cells. On the other hand, dormancy limits the acquisition and retention of spacers that trigger it. We found that the ssDNase activity of type III-A systems is required for the re-growth of a subset of the arrested cells, presumably through the degradation of the phage DNA, ending target transcription and inactivating the immune response. Altogether, our work reveals a built-in mechanism within type III-A CRISPR-Cas systems that allows the exit from dormancy needed for the subsistence of spacers that provide broad-spectrum immunity. Competing Interests: Declaration of interests LAM is a founder and scientific advisor of Intellia Therapeutics and Eligo Biosciences, and a scientific advisor to Ancilia Biosciences.
Databáze:	MEDLINE
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