tRNA Anticodon Cleavage by Target-Activated CRISPR-Cas13a Effector

Authors

Ishita Jain, Rutgers University - New Brunswick/Piscataway
Matvey Kolesnik, Skolkovo Institute of Science and Technology
Konstantin Kuznedelov, Rutgers University - New Brunswick/Piscataway
Leonid Minakhin, Rutgers University - New Brunswick/Piscataway
Natalia Morozova, Peter the Great St. Petersburg Polytechnic University
Anna Shiriaeva, Peter the Great St. Petersburg Polytechnic University
Alexandr Kirillov, Peter the Great St. Petersburg Polytechnic University
Sofia Medvedeva, Skolkovo Institute of Science and Technology
Alexei Livenskyi, Institute of Gene Biology, Moscow, Russia
Laura Kazieva, Institute of Biomedical Chemistry, Moscow, Russia
Kira S Makarova, National Library of Medicine, National Institutes of Health
Eugene V Koonin, National Library of Medicine, National Institutes of Health
Sergei Borukhov, Rowan University
Konstantin Severinov, Rutgers University - New Brunswick/Piscataway
Ekaterina Semenova, Rutgers University - New Brunswick/Piscataway

Document Type

Article

Version Deposited

Published Version

Publication Date

4-26-2024

Publication Title

Science Advances

DOI

10.1126/sciadv.adl0164

Abstract

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus providing defense from the phages. In addition, Cas13a-mediated tRNA cleavage indirectly activates the RNases of bacterial toxin-antitoxin modules cleaving messenger RNA, which could provide a backup defense. The mechanism of Cas13a-induced antiphage defense resembles that of bacterial anticodon nucleases, which is compatible with the hypothesis that type VI effectors evolved from an abortive infection module encompassing an anticodon nuclease.

Recommended Citation

Jain, Ishita; Kolesnik, Matvey; Kuznedelov, Konstantin; Minakhin, Leonid; Morozova, Natalia; Shiriaeva, Anna; Kirillov, Alexandr; Medvedeva, Sofia; Livenskyi, Alexei; Kazieva, Laura; Makarova, Kira S; Koonin, Eugene V; Borukhov, Sergei; Severinov, Konstantin; and Semenova, Ekaterina, "tRNA Anticodon Cleavage by Target-Activated CRISPR-Cas13a Effector" (2024). Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship. 209.
https://rdw.rowan.edu/som_facpub/209

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Published Citation

Jain I, Kolesnik M, Kuznedelov K, et al. tRNA anticodon cleavage by target-activated CRISPR-Cas13a effector. Science Advances. 2024 Apr 26;10(17):eadl0164. Epub 2024 Apr 24. doi: 10.1126/sciadv.adl0164. PMID: 38657076. PMCID: PMC11042736.