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Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2′-PO4 recognition and ADP-ribosylation

Author

Listed:
  • Ankan Banerjee

    (Sloan-Kettering Institute)

  • Annum Munir

    (Sloan-Kettering Institute)

  • Leonora Abdullahu

    (McGill University)

  • Masad J. Damha

    (McGill University)

  • Yehuda Goldgur

    (Sloan-Kettering Institute)

  • Stewart Shuman

    (Sloan-Kettering Institute)

Abstract

Tpt1 is an essential agent of fungal tRNA splicing that removes the 2′-PO4 at the splice junction generated by fungal tRNA ligase. Tpt1 catalyzes a unique two-step reaction whereby the 2′-PO4 attacks NAD+ to form an RNA-2′-phospho-ADP-ribosyl intermediate that undergoes transesterification to yield 2′-OH RNA and ADP-ribose-1″,2″-cyclic phosphate products. Because Tpt1 is inessential in exemplary bacterial and mammalian taxa, Tpt1 is seen as an attractive antifungal target. Here we report a 1.4 Å crystal structure of Tpt1 in a product-mimetic complex with ADP-ribose-1″-phosphate in the NAD+ site and pAp in the RNA site. The structure reveals how Tpt1 recognizes a 2′-PO4 RNA splice junction and the mechanism of RNA phospho-ADP-ribosylation. This study also provides evidence that a bacterium has an endogenous phosphorylated substrate with which Tpt1 reacts.

Suggested Citation

  • Ankan Banerjee & Annum Munir & Leonora Abdullahu & Masad J. Damha & Yehuda Goldgur & Stewart Shuman, 2019. "Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2′-PO4 recognition and ADP-ribosylation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08211-9
    DOI: 10.1038/s41467-018-08211-9
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