Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA

Sunny Sharma, Jun Yang, Ewa Grudzien-Nogalska, Jessica Shivas, Kelvin Y. Kwan and Megerditch Kiledjian ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28555-7

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