Eukaryotic RNA 5'-End NAD+ Capping and DeNADding.

A hallmark of eukaryotic mRNAs has long been the 5'-end m7G cap. This paradigm was recently amended by recent reports that Saccharomyces cerevisiae and mammalian cells also contain mRNAs carrying a novel nicotinamide adenine dinucleotide (NAD+) cap at their 5'-end. The presence of an NAD+ cap on mRNA uncovers a previously unknown mechanism for controlling gene expression through nucleotide metabolite-directed mRNA turnover. In contrast to the m7G cap that stabilizes mRNA, the NAD+ cap targets RNA for rapid decay in mammalian cells through the DXO non-canonical decapping enzyme which removes intact NAD+ from RNA in a process termed 'deNADding'. This review highlights the identification of NAD+ caps, their mode of addition, and their functional significance in cells.