IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v570y2019i7760d10.1038_s41586-019-1257-5.html
   My bibliography  Save this article

Cas13-induced cellular dormancy prevents the rise of CRISPR-resistant bacteriophage

Author

Listed:
  • Alexander J. Meeske

    (The Rockefeller University)

  • Sandra Nakandakari-Higa

    (The Rockefeller University)

  • Luciano A. Marraffini

    (The Rockefeller University
    The Rockefeller University)

Abstract

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci in prokaryotes are composed of 30–40-base-pair repeats separated by equally short sequences of plasmid and bacteriophage origin known as spacers1–3. These loci are transcribed and processed into short CRISPR RNAs (crRNAs) that are used as guides by CRISPR-associated (Cas) nucleases to recognize and destroy complementary sequences (known as protospacers) in foreign nucleic acids4,5. In contrast to most Cas nucleases, which destroy invader DNA4–7, the type VI effector nuclease Cas13 uses RNA guides to locate complementary transcripts and catalyse both sequence-specific cis- and non-specific trans-RNA cleavage8. Although it has been hypothesized that Cas13 naturally defends against RNA phages8, type VI spacer sequences have exclusively been found to match the genomes of double-stranded DNA phages9,10, suggesting that Cas13 can provide immunity against these invaders. However, whether and how Cas13 uses its cis- and/or trans-RNA cleavage activities to defend against double-stranded DNA phages is not understood. Here we show that trans-cleavage of transcripts halts the growth of the host cell and is sufficient to abort the infectious cycle. This depletes the phage population and provides herd immunity to uninfected bacteria. Phages that harbour target mutations, which easily evade DNA-targeting CRISPR systems11–13, are also neutralized when Cas13 is activated by wild-type phages. Thus, by acting on the host rather than directly targeting the virus, type VI CRISPR systems not only provide robust defence against DNA phages but also prevent outbreaks of CRISPR-resistant phage.

Suggested Citation

  • Alexander J. Meeske & Sandra Nakandakari-Higa & Luciano A. Marraffini, 2019. "Cas13-induced cellular dormancy prevents the rise of CRISPR-resistant bacteriophage," Nature, Nature, vol. 570(7760), pages 241-245, June.
  • Handle: RePEc:nat:nature:v:570:y:2019:i:7760:d:10.1038_s41586-019-1257-5
    DOI: 10.1038/s41586-019-1257-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1257-5
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-019-1257-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Antonios Apostolopoulos & Naohiro Kawamoto & Siu Yu A. Chow & Hitomi Tsuiji & Yoshiho Ikeuchi & Yuichi Shichino & Shintaro Iwasaki, 2024. "dCas13-mediated translational repression for accurate gene silencing in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Ning Cui & Jun-Tao Zhang & Zhuolin Li & Xiao-Yu Liu & Chongyuan Wang & Hongda Huang & Ning Jia, 2022. "Structural basis for the non-self RNA-activated protease activity of the type III-E CRISPR nuclease-protease Craspase," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Gabriel Magno Freitas Almeida & Ville Hoikkala & Janne Ravantti & Noora Rantanen & Lotta-Riina Sundberg, 2022. "Mucin induces CRISPR-Cas defense in an opportunistic pathogen," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Lidiya Lisitskaya & Yeonoh Shin & Aleksei Agapov & Anna Olina & Ekaterina Kropocheva & Sergei Ryazansky & Alexei A. Aravin & Daria Esyunina & Katsuhiko S. Murakami & Andrey Kulbachinskiy, 2022. "Programmable RNA targeting by bacterial Argonaute nucleases with unconventional guide binding and cleavage specificity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:570:y:2019:i:7760:d:10.1038_s41586-019-1257-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.