NUDT16 (3q22.1), RNA decapping pathway, IDPphosphatase

https://www.ncbi.nlm.nih.gov/gene/131870 

Preferred Names

U8 snoRNA-decapping enzyme

Names

IDP phosphatase

IDPase

U8 snoRNA-binding protein H29K

inosine diphosphate phosphatase

m7GpppN-mRNA hydrolase

nucleoside diphosphate-linked moiety X motif 16

nudix (nucleoside diphosphate linked moiety X)-type motif 16

nudix motif 16

testicular tissue protein Li 129

NP_001165376.1

• EC 3.6.1.62

• EC 3.6.1.64

Structure, history 

Conserved Domains (1) summary

cl00447
Location:7 → 36

Nudix_Hydrolase; Nudix hydrolase is a superfamily of enzymes found in all three kingdoms of life, and it catalyzes the hydrolysis of NUcleoside DIphosphates linked to other moieties, X. Enzymes belonging to this superfamily require a divalent cation, such as Mg2+ or Mn2+ ...

Related articles in PubMed

1. Hydrolytic activity of human Nudt16 enzyme on dinucleotide cap analogs and short capped oligonucleotides. Grzela R, et al. RNA, 2018 May. PMID 29483298,
2. Virus-induced translational arrest through 4EBP1/2-dependent decay of 5'-TOP mRNAs restricts viral infection. Hopkins KC, et al. Proc Natl Acad Sci U S A, 2015 Jun 2. PMID 26038567, Free PMC Article
3. Crystallization and crystallographic analysis of human NUDT16. Zhang J, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2008 Jul 1. PMID 18607096, Free PMC Article
4. Epigenetic loss of the RNA decapping enzyme NUDT16 mediates C-MYC activation in T-cell acute lymphoblastic leukemia. Anadón C, et al. Leukemia, 2017 Jul. PMID 28344317, Free PMC Article
5. Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate. Trésaugues L, et al. PLoS One, 2015. PMID 26121039, Free PMC Article

See all (20) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. hNudt16 hydrolysis of dinucleotide cap analogs and short capped oligonucleotides displayed a broader spectrum specificity than is currently known.
2. data suggest the existence in T-ALL of a disrupted RNA decapping pathway, mediated by the DNA methylation-associated loss of NUDT16, which contributes to the natural history of the disease by stabilizing transforming factors, such as is the case of the leukemogenic protein C-MYC
3. This study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16.
4. The RNA decapping enzyme NUDT16 selectively degrades 5'-TOP mRNAs during Rift Valley fever virus infection and this decay is triggered in response to mTOR attenuation via the translational repressor 4EBP1/2 axis.
5. hNUDT16 can also actively cleave the mGDP cap from mRNAs in the presence of Mg(2)(+) or Mn(2)(+).
6. Like Dcp2, Nudt16 also regulates the stability of a subset of mRNAs including a member of the motin family of proteins involved in angiogenesis.
7. NUDT16 is a (deoxy)inosine diphosphatase that may function mainly in the nucleus to protect cells from deleterious effects of (d)ITP.
8. Recombinant NUDT16, a decapping enzyme, has been crystallized. NUDT16 plays a pivotal role in U8 snoRNA stability.
9. X29/H29K may be the nuclear counterparts of the cytoplasmic decapping machinery, localized in specialized bodies involved in RNA decay

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(1) Citate

RNA. 2018 May;24(5):633-642. doi: 10.1261/rna.065698.118. Epub 2018 Feb 26.

Hydrolytic activity of human Nudt16 enzyme on dinucleotide cap analogs and short capped oligonucleotides.

Grzela R¹, Nasilowska K², Lukaszewicz M², Tyras M¹, Stepinski J¹, Jankowska-Anyszka M³, Bojarska E¹, Darzynkiewicz E^1,2. Abstract

Human Nudt16 (hNudt16) is a member of the Nudix family of hydrolases, comprising enzymes catabolizing various substrates including canonical (d)NTPs, oxidized (d)NTPs, nonnucleoside polyphosphates, and capped mRNAs.
 Decapping activity of the Xenopus laevis (X29) Nudt16 homolog was observed in the nucleolus, with a high specificity toward U8 snoRNA. Subsequent studies have reported cytoplasmic localization of mammalian Nudt16 with cap hydrolysis activity initiating RNA turnover, similar to Dcp2. The present study focuses on hNudt16 and its hydrolytic activity toward dinucleotide cap analogs and short capped oligonucleotides.
 We performed a screening assay for potential dinucleotide and oligonucleotide substrates for hNudt16. Our data indicate that dinucleotide cap analogs and capped oligonucleotides containing guanine base in the first transcribed nucleotide are more susceptible to enzymatic digestion by hNudt16 than their counterparts containing adenine. Furthermore, unmethylated dinucleotides (GpppG and ApppG) and respective oligonucleotides (GpppG-16nt and GpppA-16nt) were hydrolyzed by hNudt16 with greater efficiency than were m⁷GpppG and m⁷GpppG-16nt. In conclusion, we found that hNudt16 hydrolysis of dinucleotide cap analogs and short capped oligonucleotides displayed a broader spectrum specificity than is currently known.

KEYWORDS: cap analogs; cap hydrolysis; capped oligonucleotides; decapping enzymes; nudix hydrolasesPMID:29483298 PMCID: PMC5900562[Available on 2019-05-01] DOI:10.1261/rna.065698.118

 (9) Citate.

J Biol Chem. 2007 Aug 24;282(34):24792-805. Epub 2007 Jun 13.

Metal determines efficiency and substrate specificity of the nuclear NUDIX decapping proteins X29 and H29K (Nudt16).

Peculis BA¹, Reynolds K, Cleland M. Abstract

The Xenopus X29 protein was identified by its high affinity binding to U8 small nucleolar RNA, a small nucleolar RNA required for ribosome biogenesis. X29 and its human homologue H29K (Nudt16) are nuclear nucleoside diphosphatase proteins localized within foci in the nucleolus and nucleoplasm. These proteins can remove m(7)G and m(227)G caps from RNAs, rendering them substrates for 5'-3' exonucleases for degradation in vivo. Here, a more complete characterization of these metal-dependent decapping proteins demonstrates that the metal identity determines both the efficiency of decapping and the RNA substrate specificity. In Mg(+2) the proteins hydrolyze the 5' cap from only one RNA substrate: U8 small nucleolar RNA. However, in the presence of Mn(+2) or Co(+2) all RNAs are substrates and the decapping efficiency is higher. The x-ray crystal structure of X29 facilitated structure-based mutagenesis. Mutation of single amino acids coordinating metal in the active site yielded mutant proteins confirming essential residues. In vitro assays with purified components are consistent with a lack of protein turnover, apparently due to an inability of the protein to release the decapped RNA, implicating critical in vivo interacting factors. Collectively, these studies indicate that the metal that binds the X29/H29K proteins in vivo may determine whether these decapping proteins function solely as a negative regulator of ribosome biogenesis or can decap a wider variety of nuclear-limited RNAs. With the potential broader RNA substrate specificity, X29/H29K may be the nuclear counterparts of the cytoplasmic decapping machinery, localized in specialized bodies involved in RNA decay. PMID: 17567574 DOI: 10.1074/jbc.M704179200[Indexed for MEDLINE] Free full text