Bacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs
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Bacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs. / Camara-Wilpert, Sarah; Mayo-Muñoz, David; Russel, Jakob; Fagerlund, Robert D.; Madsen, Jonas S.; Fineran, Peter C.; Sørensen, Søren J.; Pinilla-Redondo, Rafael.
In: Nature, Vol. 623, No. 7987, 2023, p. 601-607.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Bacteriophages suppress CRISPR–Cas immunity using RNA-based anti-CRISPRs
AU - Camara-Wilpert, Sarah
AU - Mayo-Muñoz, David
AU - Russel, Jakob
AU - Fagerlund, Robert D.
AU - Madsen, Jonas S.
AU - Fineran, Peter C.
AU - Sørensen, Søren J.
AU - Pinilla-Redondo, Rafael
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Many bacteria use CRISPR–Cas systems to combat mobile genetic elements, such as bacteriophages and plasmids1. In turn, these invasive elements have evolved anti-CRISPR proteins to block host immunity2,3. Here we unveil a distinct type of CRISPR–Cas Inhibition strategy that is based on small non-coding RNA anti-CRISPRs (Racrs). Racrs mimic the repeats found in CRISPR arrays and are encoded in viral genomes as solitary repeat units4. We show that a prophage-encoded Racr strongly inhibits the type I-F CRISPR–Cas system by interacting specifically with Cas6f and Cas7f, resulting in the formation of an aberrant Cas subcomplex. We identified Racr candidates for almost all CRISPR–Cas types encoded by a diverse range of viruses and plasmids, often in the genetic context of other anti-CRISPR genes5. Functional testing of nine candidates spanning the two CRISPR–Cas classes confirmed their strong immune inhibitory function. Our results demonstrate that molecular mimicry of CRISPR repeats is a widespread anti-CRISPR strategy, which opens the door to potential biotechnological applications6.
AB - Many bacteria use CRISPR–Cas systems to combat mobile genetic elements, such as bacteriophages and plasmids1. In turn, these invasive elements have evolved anti-CRISPR proteins to block host immunity2,3. Here we unveil a distinct type of CRISPR–Cas Inhibition strategy that is based on small non-coding RNA anti-CRISPRs (Racrs). Racrs mimic the repeats found in CRISPR arrays and are encoded in viral genomes as solitary repeat units4. We show that a prophage-encoded Racr strongly inhibits the type I-F CRISPR–Cas system by interacting specifically with Cas6f and Cas7f, resulting in the formation of an aberrant Cas subcomplex. We identified Racr candidates for almost all CRISPR–Cas types encoded by a diverse range of viruses and plasmids, often in the genetic context of other anti-CRISPR genes5. Functional testing of nine candidates spanning the two CRISPR–Cas classes confirmed their strong immune inhibitory function. Our results demonstrate that molecular mimicry of CRISPR repeats is a widespread anti-CRISPR strategy, which opens the door to potential biotechnological applications6.
U2 - 10.1038/s41586-023-06612-5
DO - 10.1038/s41586-023-06612-5
M3 - Journal article
C2 - 37853129
AN - SCOPUS:85174388713
VL - 623
SP - 601
EP - 607
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 7987
ER -
ID: 385898997