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.

• DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs.

  Doamekpor S.K., Grudzien-Nogalska E., Mlynarska-Cieslak A., Kowalska J., Kiledjian M., Tong L.

  In eukaryotes, the DXO/Rai1 enzymes can eliminate most of the incomplete and non-canonical NAD caps through their decapping, deNADding and pyrophosphohydrolase activities. Here, we report that these enzymes can also remove FAD and dephospho-CoA (dpCoA) non-canonical caps from RNA, and we have name ... >> More

  In eukaryotes, the DXO/Rai1 enzymes can eliminate most of the incomplete and non-canonical NAD caps through their decapping, deNADding and pyrophosphohydrolase activities. Here, we report that these enzymes can also remove FAD and dephospho-CoA (dpCoA) non-canonical caps from RNA, and we have named these activities deFADding and deCoAping. The crystal structures of mammalian DXO with 3'-FADP or CoA and fission yeast Rai1 with 3'-FADP provide elegant insight to these activities. FAD and CoA are accommodated in the DXO/Rai1 active site by adopting folded conformations. The flavin of FAD and the pantetheine group of CoA contact the same region at the bottom of the active site tunnel, which undergoes conformational changes to accommodate the different cap moieties. We have developed FAD-capQ to detect and quantify FAD-capped RNAs and determined that FAD caps are present on short RNAs (with less than ∼200 nucleotides) in human cells and that these RNAs are stabilized in the absence of DXO. << Less

  Nucleic Acids Res. 48:6136-6148(2020) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.