Publications

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

  Kiledjian M.

  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 presen ... >> More

  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. << Less

  Trends Cell Biol 28:454-464(2018) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• 5' end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding.

  Jiao X., Doamekpor S.K., Bird J.G., Nickels B.E., Tong L., Hart R.P., Kiledjian M.

  Eukaryotic mRNAs generally possess a 5' end N7 methyl guanosine (m⁷G) cap that promotes their translation and stability. However, mammalian mRNAs can also carry a 5' end nicotinamide adenine dinucleotide (NAD⁺) cap that, in contrast to the m⁷G cap, does not support ... >> More

  Eukaryotic mRNAs generally possess a 5' end N7 methyl guanosine (m⁷G) cap that promotes their translation and stability. However, mammalian mRNAs can also carry a 5' end nicotinamide adenine dinucleotide (NAD⁺) cap that, in contrast to the m⁷G cap, does not support translation but instead promotes mRNA decay. The mammalian and fungal noncanonical DXO/Rai1 decapping enzymes efficiently remove NAD⁺ caps, and cocrystal structures of DXO/Rai1 with 3'-NADP⁺ illuminate the molecular mechanism for how the "deNADding" reaction produces NAD⁺ and 5' phosphate RNA. Removal of DXO from cells increases NAD⁺-capped mRNA levels and enables detection of NAD⁺-capped intronic small nucleolar RNAs (snoRNAs), suggesting NAD⁺ caps can be added to 5'-processed termini. Our findings establish NAD⁺ as an alternative mammalian RNA cap and DXO as a deNADding enzyme modulating cellular levels of NAD⁺-capped RNAs. Collectively, these data reveal that mammalian RNAs can harbor a 5' end modification distinct from the classical m⁷G cap that promotes rather than inhibits RNA decay. << Less

  Cell 168:1015-1027(2017) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.