Viral proteins activate PARIS-mediated tRNA degradation and viral tRNAs rescue infection

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Abstract

Viruses compete with each other for limited cellular resources, and some viruses deliver defense mechanisms that protect the host from competing genetic parasites. PARIS is a defense system, often encoded in viral genomes, that is composed of a 53 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB). Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving the host tRNA Lys . Phage T5 subverts PARIS immunity through expression of a tRNA Lys variant that prevents PARIS-mediated cleavage, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids.

Article activity feed

  1. Brianna Duncan-Lowey

    Review 3: "Viral Proteins Activate PARIS-Mediated tRNA Degradation and Viral tRNAs Rescue Infection"

    Reviewers offered strong support for this manuscript characterizing the PARIS bacterial immune system, praising the compelling multi-disciplinary evidence presented on the mechanism of PARIS activation and tRNA degradation to induce viral infection abortion.

  2. David Taylor, Jack Bravo

    Review 2: "Viral Proteins Activate PARIS-Mediated tRNA Degradation and Viral tRNAs Rescue Infection"

    Reviewers offered strong support for this manuscript characterizing the PARIS bacterial immune system, praising the compelling multi-disciplinary evidence presented on the mechanism of PARIS activation and tRNA degradation to induce viral infection abortion.

  3. Sukrit Silas

    Review 1: "Viral Proteins Activate PARIS-Mediated tRNA Degradation and Viral tRNAs Rescue Infection"

    Reviewers offered strong support for this manuscript characterizing the PARIS bacterial immune system, praising the compelling multi-disciplinary evidence presented on the mechanism of PARIS activation and tRNA degradation to induce viral infection abortion.

  4. Strength of evidence

    Reviewers: S Silas (UC San Francisco) | ๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜
    D Taylor (UT Austin) & J Bravo (UT Austin) | ๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜
    B Duncan-Lowey (Yale University)| ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ