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Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA

Author

Listed:
  • Sunny Sharma

    (Rutgers University)

  • Jun Yang

    (Rutgers University)

  • Ewa Grudzien-Nogalska

    (Rutgers University)

  • Jessica Shivas

    (Rutgers University)

  • Kelvin Y. Kwan

    (Rutgers University)

  • Megerditch Kiledjian

    (Rutgers University)

Abstract

The existence of non-canonical nicotinamide adenine diphosphate (NAD) 5′-end capped RNAs is now well established. Nevertheless, the biological function of this nucleotide metabolite cap remains elusive. Here, we show that the yeast Saccharomyces cerevisiae cytoplasmic 5′-end exoribonuclease Xrn1 is also a NAD cap decapping (deNADding) enzyme that releases intact NAD and subsequently degrades the RNA. The significance of Xrn1 deNADding is evident in a deNADding deficient Xrn1 mutant that predominantly still retains its 5′-monophosphate exonuclease activity. This mutant reveals Xrn1 deNADding is necessary for normal growth on non-fermenting sugar and is involved in modulating mitochondrial NAD-capped RNA levels and may influence intramitochondrial NAD levels. Our findings uncover a contribution of mitochondrial NAD-capped RNAs in overall NAD regulation with the deNADding activity of Xrn1 fulfilling a central role.

Suggested Citation

  • Sunny Sharma & Jun Yang & Ewa Grudzien-Nogalska & Jessica Shivas & Kelvin Y. Kwan & Megerditch Kiledjian, 2022. "Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28555-7
    DOI: 10.1038/s41467-022-28555-7
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    1. Xufeng Wang & Dongli Yu & Jiancheng Yu & Hao Hu & Runlai Hang & Zachary Amador & Qi Chen & Jijie Chai & Xuemei Chen, 2024. "Toll/interleukin-1 receptor (TIR) domain-containing proteins have NAD-RNA decapping activity," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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