Abstract
A hallmark of eukaryotic mRNAs has long been the 5'-end m(7)G 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 m(7)G 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.