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bioRxiv · 10.1101/2021.06.25.449970

Xrn1 is a deNADding Enzyme Modulating Mitochondrial NAD Levels

Sharma, S.·Yang, J.·Grudzien Nogalska, E.·Kiledjian, M.
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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 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 in turn intramitochondrial NAD levels. Our findings uncover a functional role for mitochondrial NAD-capped RNAs as a reservoir to maintain overall NAD homeostasis. We propose NAD-capped RNAs function as a cistern for mitochondrial NAD with Xrn1 serving as a rheostat for NAD-capped RNAs.

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Sharma, S., Yang, J., Grudzien Nogalska, E., Kiledjian, M.. 2021-06-25. Xrn1 is a deNADding Enzyme Modulating Mitochondrial NAD Levels. https://doi.org/10.1101/2021.06.25.449970

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