Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
accepted:
05
05
2020
revised:
01
05
2020
received:
30
03
2020
pubmed:
21
5
2020
medline:
9
9
2020
entrez:
21
5
2020
Statut:
ppublish
Résumé
We recently reported the presence of nicotinamide adenine dinucleotide (NAD)-capped RNAs in mammalian cells and a role for DXO and the Nudix hydrolase Nudt12 in decapping NAD-capped RNAs (deNADding) in cells. Analysis of 5'caps has revealed that in addition to NAD, mammalian RNAs also contain other metabolite caps including flavin adenine dinucleotide (FAD) and dephosphoCoA (dpCoA). In the present study we systematically screened all mammalian Nudix proteins for their potential deNADing, FAD cap decapping (deFADding) and dpCoA cap decapping (deCoAping) activity. We demonstrate that Nudt16 is a novel deNADding enzyme in mammalian cells. Additionally, we identified seven Nudix proteins-Nudt2, Nudt7, Nudt8, Nudt12, Nudt15, Nudt16 and Nudt19, to possess deCoAping activity in vitro. Moreover, our screening revealed that both mammalian Nudt2 and Nudt16 hydrolyze FAD-capped RNAs in vitro with Nudt16 regulating levels of FAD-capped RNAs in cells. All decapping activities identified hydrolyze the metabolite cap substrate within the diphosphate linkage. Crystal structure of human Nudt16 in complex with FAD at 2.7 Å resolution provide molecular insights into the binding and metal-coordinated hydrolysis of FAD by Nudt16. In summary, our study identifies novel cellular deNADding and deFADding enzymes and establishes a foundation for the selective functionality of the Nudix decapping enzymes on non-canonical metabolite caps.
Identifiants
pubmed: 32432673
pii: 5841131
doi: 10.1093/nar/gkaa402
pmc: PMC7337524
doi:
Substances chimiques
RNA Caps
0
NAD
0U46U6E8UK
Flavin-Adenine Dinucleotide
146-14-5
dephosphocoenzyme A
3633-59-8
NUDT15 protein, human
EC 2.6.1.-
Phosphoric Monoester Hydrolases
EC 3.1.3.2
NUDT12 protein, human
EC 3.6.1.-
Nudt16 protein, human
EC 3.6.1.-
Pyrophosphatases
EC 3.6.1.-
NUDT2 protein, human
EC 3.6.1.17
Coenzyme A
SAA04E81UX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6788-6798Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM067005
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126488
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118093
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103403
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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