5ULI

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

(2017) Cell 168: 1015-1027.e10

• PubMed: 28283058 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1016/j.cell.2017.02.019
• Primary Citation of Related Structures:  
  5ULI, 5ULJ


• PubMed 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.

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Organizational Affiliation: 

Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.