5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding
| Autor: | Xinfu Jiao, Megerditch Kiledjian, Ronald P. Hart, Selom K. Doamekpor, Liang Tong, Bryce E. Nickels, Jeremy G. Bird |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA Stability RNA Untranslated Guanosine Biology Nicotinamide adenine dinucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound Mice Endoribonucleases Protein biosynthesis Animals Humans RNA Messenger Small nucleolar RNA RNA Processing Post-Transcriptional RNA Nuclear Proteins Translation (biology) NAD 030104 developmental biology HEK293 Cells Biochemistry chemistry Protein Biosynthesis NAD+ kinase |
| Zdroj: | Cell. 168(6) |
| ISSN: | 1097-4172 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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