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Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs.

Wu H, Li L, Chen KM, Homolka D, Gos P, Fleury-Olela F, McCarthy AA, Pillai RS
Cell Rep 29 4422-4434.e13 (2019)
Cited: 14 times
EuropePMC logo PMID: 31875550

Abstract

RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs.

Articles - 6scx mentioned but not cited (2)

  1. In silico Druggability Assessment of the NUDIX Hydrolase Protein Family as a Workflow for Target Prioritization. Michel M, Homan EJ, Wiita E, Pedersen K, Almlöf I, Gustavsson AL, Lundbäck T, Helleday T, Warpman Berglund U. Front Chem 8 443 (2020)
  2. Structural insights into dpCoA-RNA decapping by NudC. Zhou W, Guan Z, Zhao F, Ye Y, Yang F, Yin P, Zhang D. RNA Biol 18 244-253 (2021)


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  1. The potential role of N7-methylguanosine (m7G) in cancer. Luo Y, Yao Y, Wu P, Zi X, Sun N, He J. J Hematol Oncol 15 63 (2022)
  2. Recent insights into noncanonical 5' capping and decapping of RNA. Doamekpor SK, Sharma S, Kiledjian M, Tong L. J Biol Chem 298 102171 (2022)
  3. The use of RNA-based treatments in the field of cancer immunotherapy. Chehelgerdi M, Chehelgerdi M. Mol Cancer 22 106 (2023)

Articles citing this publication (9)

  1. InsP7 is a small-molecule regulator of NUDT3-mediated mRNA decapping and processing-body dynamics. Sahu S, Wang Z, Jiao X, Gu C, Jork N, Wittwer C, Li X, Hostachy S, Fiedler D, Wang H, Jessen HJ, Kiledjian M, Shears SB. Proc Natl Acad Sci U S A 117 19245-19253 (2020)
  2. Substrate Specificity of SARS-CoV-2 Nsp10-Nsp16 Methyltransferase. Benoni R, Krafcikova P, Baranowski MR, Kowalska J, Boura E, Cahová H. Viruses 13 1722 (2021)
  3. Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs. Sharma S, Grudzien-Nogalska E, Hamilton K, Jiao X, Yang J, Tong L, Kiledjian M. Nucleic Acids Res 48 6788-6798 (2020)
  4. A Poxvirus Decapping Enzyme Colocalizes with Mitochondria To Regulate RNA Metabolism and Translation and Promote Viral Replication. Cao S, Molina JA, Cantu F, Hernandez C, Yang Z. mBio 13 e0030022 (2022)
  5. miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation. Zhang Q, Yan YF, Lv Q, Li YJ, Wang RR, Sun GB, Pan L, Hu JX, Xie N, Zhang C, Tian BC, Jiao F, Xu S, Wang PY, Xie SY. Cell Death Dis 12 735 (2021)
  6. Meta-analysis of Diurnal Transcriptomics in Mouse Liver Reveals Low Repeatability of Rhythm Analyses. Brooks TG, Manjrekar A, Mrcˇela A, Grant GR. J Biol Rhythms 38 556-570 (2023)
  7. Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions. He J, Lin H, Ding Y, Liu X, Xu K, Chen X, Shen W, Zhou S, Wang M, Xia J, He N. J Transl Med 20 609 (2022)
  8. Identification of novel N7-methylguanine-related gene signatures associated with ulcerative colitis and the association with biological therapy. Yang L, Yuan L. Inflamm Res 72 2169-2180 (2023)
  9. Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target. Duarte-Pereira S, Matos S, Oliveira JL, Silva RM. J Integr Bioinform 20 (2023)


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