GBM Lunch

Sunny Sharma: NAD-Capped RNAs act a reservoir for intramitochondrial NAD


Sunny Sharma


Speaker: Sunny Sharma, Department of Cell Biology and Neurosciences, Rutgers University, Piscataway,New Jersey, USA

Chair: Andreas Schlundt, Goethe University Frankfurt, Institute for Molecular Biosciences

Organizers: AK Young Investigators

The presence of non-canonical nicotinamide adenine diphosphate (NAD) 5´-end capped RNAs has now been well established with a disproportionally high level of NAD-capped RNAs in mitochondrial. Nevertheless, the biological function of this nucleotide metabolite cap remains elusive. Here, we show that mitochondrial NAD-capped RNAs can serve as a reservoir to maintain overall mitochondrial NAD homeostasis in the yeast Saccharomyces cerevisiae. We identify two exoribonucleases to be specifically associated with the NAD cap. Both proteins possess NAD cap decapping (deNADding) activity to release intact NAD and subsequently degrade the RNA. Yeast cells harboring a deNADding deficient mutant demonstrate that deNADing is necessary for normal growth under non-fermenting sugar and is involved in modulating levels of mitochondrial NAD-capped RNAs and intramitochondrial NAD levels. We propose that NAD capped RNAs function as a cistern for mitochondrial NAD with exoribonucleases serving as a gatekeeper to release NAD from NAD-capped RNAs.