Reference - PMID:28283058 - 5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.
Reference summary
- PubMed ID
- PMID:28283058
- Title
- 5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.
- Authors
- Jiao X, Doamekpor SK, Bird JG, Nickels BE, Tong L, Hart RP, Kiledjian M
- Citation
- Cell 2017 Mar 09;168(6):1015-1027.e10
- Publication year
- 2017
- Abstract
- Eukaryotic mRNAs generally possess a 5' end N7 methyl guanosine (m 7 G) 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 m 7 G 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 m 7 G cap that promotes rather than inhibits RNA decay.
