| First Author | Jiao X | Year | 2017 |
| Journal | Cell | Volume | 168 |
| Issue | 6 | Pages | 1015-1027.e10 |
| PubMed ID | 28283058 | Mgi Jnum | J:279953 |
| Mgi Id | MGI:6368104 | Doi | 10.1016/j.cell.2017.02.019 |
| Citation | Jiao X, et al. (2017) 5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding. Cell 168(6):1015-1027.e10 |
| abstractText | 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. |
