5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.

ABSTRACT: 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 NA

SUBMITTER: Jiao X 

PROVIDER: S-EPMC5371429 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature