Structural and mechanistic basis of mammalian Nudt12 RNA deNADding

Grudzien-Nogalska, Ewa; Wu, Yixuan; Jiao, Xinfu; Cui, Huijuan; Mateyak, Maria K.; Hart, Ronald P.; Tong, Liang; Kiledjian, Megerditch

doi:10.1038/s41589-019-0293-7

Title: Structural and mechanistic basis of mammalian Nudt12 RNA deNADding

Journal Article · Fri May 17 00:00:00 EDT 2019 · Nature Chemical Biology

DOI:https://doi.org/10.1038/s41589-019-0293-7· OSTI ID:1531008

Grudzien-Nogalska, Ewa ^[1]; Wu, Yixuan ^[2]; Jiao, Xinfu ^[1]; Cui, Huijuan ^[1]; Mateyak, Maria K. ^[1]; Hart, Ronald P. ^[1];

^[2];

^[1]

Rutgers Univ., Piscataway, NJ (United States)
Columbia Univ., New York, NY (United States)

We recently demonstrated that mammalian cells harbor nicotinamide adenine dinucleotide (NAD)-capped messenger RNAs that are hydrolyzed by the DXO deNADding enzyme. Here, we report that the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targeting different RNAs. Here, the crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg²⁺ ions at 1.6 Å resolution provides insights into the molecular basis of the deNADding activity in the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells, and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to nutrient or environmental stress manifests changes in NAD-capped RNA levels that are selectively responsive to Nudt12 or DXO, respectively, indicating an association of deNADding to cellular metabolism.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH); NIH-ORIP HEI

Grant/Contract Number:: AC02-06CH11357; GM118093; S10OD012018; GM126488; P41 GM103403; S10 RR029205

OSTI ID:: 1531008

Journal Information:: Nature Chemical Biology, Vol. 15, Issue 6; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 34 works

Citation information provided by
Web of Science

References (50)

Edc3 Function in Yeast and Mammals Is Modulated by Interaction with NAD-Related Compounds Walters, Robert W.; Shumilin, Igor A.; Yoon, Je-Hyun G3: Genes\|Genomes\|Genetics, Vol. 4, Issue 4 https://doi.org/10.1534/g3.114.010470	journal	February 2014
Superior 5' homogeneity of RNA from ATP-initiated transcription under the T7 2.5 promoter Coleman, T. M. Nucleic Acids Research, Vol. 32, Issue 1 https://doi.org/10.1093/nar/gnh007	journal	January 2004
Ribonuclease E is a 5′-end-dependent endonuclease Mackie, George A. Nature, Vol. 395, Issue 6703 https://doi.org/10.1038/27246	journal	October 1998
Mouse Nudt13 is a Mitochondrial Nudix Hydrolase with NAD(P)H Pyrophosphohydrolase Activity Abdelraheim, Salama R.; Spiller, David G.; McLennan, Alexander G. The Protein Journal, Vol. 36, Issue 5 https://doi.org/10.1007/s10930-017-9734-x	journal	July 2017
Capture and sequencing of NAD-capped RNA sequences with NAD captureSeq Winz, Marie-Luise; Cahová, Hana; Nübel, Gabriele Nature Protocols, Vol. 12, Issue 1 https://doi.org/10.1038/nprot.2016.163	journal	December 2016
Glucose Restriction Inhibits Skeletal Myoblast Differentiation by Activating SIRT1 through AMPK-Mediated Regulation of Nampt Fulco, Marcella; Cen, Yana; Zhao, Po Developmental Cell, Vol. 14, Issue 5 https://doi.org/10.1016/j.devcel.2008.02.004	journal	May 2008
Functional Link between the Mammalian Exosome and mRNA Decapping Wang, Zuoren; Kiledjian, Megerditch Cell, Vol. 107, Issue 6 https://doi.org/10.1016/S0092-8674(01)00592-X	journal	December 2001
A Mammalian Pre-mRNA 5′ End Capping Quality Control Mechanism and an Unexpected Link of Capping to Pre-mRNA Processing Jiao, Xinfu; Chang, Jeong Ho; Kilic, Turgay Molecular Cell, Vol. 50, Issue 1 https://doi.org/10.1016/j.molcel.2013.02.017	journal	April 2013
The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA Bird, Jeremy G.; Zhang, Yu; Tian, Yuan Nature, Vol. 535, Issue 7612 https://doi.org/10.1038/nature18622	journal	July 2016
Identification of NAD ⁺ capped mRNAs in Saccharomyces cerevisiae Walters, Robert W.; Matheny, Tyler; Mizoue, Laura S. Proceedings of the National Academy of Sciences, Vol. 114, Issue 3 https://doi.org/10.1073/pnas.1619369114	journal	December 2016
Eukaryotic RNA 5′-End NAD + Capping and DeNADding Kiledjian, Megerditch Trends in Cell Biology, Vol. 28, Issue 6 https://doi.org/10.1016/j.tcb.2018.02.005	journal	June 2018
Multiple Nudix family proteins possess mRNA decapping activity Song, M. -G.; Bail, S.; Kiledjian, M. RNA, Vol. 19, Issue 3 https://doi.org/10.1261/rna.037309.112	journal	January 2013
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Multiple mRNA Decapping Enzymes in Mammalian Cells Song, Man-Gen; Li, You; Kiledjian, Megerditch Molecular Cell, Vol. 40, Issue 3 https://doi.org/10.1016/j.molcel.2010.10.010	journal	November 2010
NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs Cahová, Hana; Winz, Marie-Luise; Höfer, Katharina Nature, Vol. 519, Issue 7543 https://doi.org/10.1038/nature14020	journal	December 2014
“NAD-capQ” detection and quantitation of NAD caps Grudzien-Nogalska, Ewa; Bird, Jeremy G.; Nickels, Bryce E. RNA, Vol. 24, Issue 10 https://doi.org/10.1261/rna.067686.118	journal	July 2018
IRF-3-dependent and augmented target genes during viral infection Andersen, J.; VanScoy, S.; Cheng, T-F Genes & Immunity, Vol. 9, Issue 2 https://doi.org/10.1038/sj.gene.6364449	journal	December 2007
Transfer-PCR (TPCR): A highway for DNA cloning and protein engineering Erijman, Ariel; Dantes, Ada; Bernheim, Reut Journal of Structural Biology, Vol. 175, Issue 2 https://doi.org/10.1016/j.jsb.2011.04.005	journal	August 2011
Identification of a quality-control mechanism for mRNA 5′-end capping Jiao, Xinfu; Xiang, Song; Oh, ChanSeok Nature, Vol. 467, Issue 7315 https://doi.org/10.1038/nature09338	journal	August 2010
Cloning, Purification, and Properties of a Novel NADH Pyrophosphatase: EVIDENCE FOR A NUCLEOTIDE PYROPHOSPHATASE CATALYTIC DOMAIN IN MutT-LIKE ENZYMES Frick, David N.; Bessman, Maurice J. Journal of Biological Chemistry, Vol. 270, Issue 4 https://doi.org/10.1074/jbc.270.4.1529	journal	January 1995
Structural basis of prokaryotic NAD-RNA decapping by NudC Zhang, Delin; Liu, Yexing; Wang, Qiang Cell Research, Vol. 26, Issue 9 https://doi.org/10.1038/cr.2016.98	journal	August 2016
5′ End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding Jiao, Xinfu; Doamekpor, Selom K.; Bird, Jeremy G. Cell, Vol. 168, Issue 6 https://doi.org/10.1016/j.cell.2017.02.019	journal	March 2017
Tissue-specific regulation of SIRT1 by calorie restriction Chen, D.; Bruno, J.; Easlon, E. Genes & Development, Vol. 22, Issue 13 https://doi.org/10.1101/gad.1650608	journal	July 2008
LC/MS analysis of cellular RNA reveals NAD-linked RNA Chen, Y. Grace; Kowtoniuk, Walter E.; Agarwal, Isha Nature Chemical Biology, Vol. 5, Issue 12 https://doi.org/10.1038/nchembio.235	journal	October 2009
Structure and function of the bacterial decapping enzyme NudC Höfer, Katharina; Li, Sisi; Abele, Florian Nature Chemical Biology, Vol. 12, Issue 9 https://doi.org/10.1038/nchembio.2132	journal	July 2016
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity Cantó, Carles; Gerhart-Hines, Zachary; Feige, Jerome N. Nature, Vol. 458, Issue 7241 https://doi.org/10.1038/nature07813	journal	March 2009
Mammalian NADH diphosphatases of the Nudix family: cloning and characterization of the human peroxisomal NUDT12 protein Abdelraheim, Salama R.; Spiller, David G.; McLENNAN, Alexander G. Biochemical Journal, Vol. 374, Issue 2 https://doi.org/10.1042/bj20030441	journal	September 2003
Identification, Biosynthesis, and Decapping of NAD-Capped RNAs in B. subtilis Frindert, Jens; Zhang, Yaqing; Nübel, Gabriele Cell Reports, Vol. 24, Issue 7 https://doi.org/10.1016/j.celrep.2018.07.047	journal	August 2018
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/S0907444902016657	journal	October 2002
Interdependence of AMPK and SIRT1 for Metabolic Adaptation to Fasting and Exercise in Skeletal Muscle Cantó, Carles; Jiang, Lake Q.; Deshmukh, Atul S. Cell Metabolism, Vol. 11, Issue 3 https://doi.org/10.1016/j.cmet.2010.02.006	journal	March 2010
A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family Carreras-Puigvert, Jordi; Zitnik, Marinka; Jemth, Ann-Sofie Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01642-w	journal	November 2017
Bacterial RNA polymerase caps RNA with various cofactors and cell wall precursors Julius, Christina; Yuzenkova, Yulia Nucleic Acids Research, Vol. 45, Issue 14 https://doi.org/10.1093/nar/gkx452	journal	May 2017
Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks Trapnell, Cole; Roberts, Adam; Goff, Loyal Nature Protocols, Vol. 7, Issue 3 https://doi.org/10.1038/nprot.2012.016	journal	March 2012
Functional characterization of the mammalian mRNA decapping enzyme hDcp2 Piccirillo, C. RNA, Vol. 9, Issue 9 https://doi.org/10.1261/rna.5690503	journal	September 2003
The SIRT1 Modulators AROS and DBC1 Regulate HSF1 Activity and the Heat Shock Response Raynes, Rachel; Pombier, Kathleen M.; Nguyen, Kevin PLoS ONE, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pone.0054364	journal	January 2013
Structures and mechanisms of Nudix hydrolases Mildvan, A. S.; Xia, Z.; Azurmendi, H. F. Archives of Biochemistry and Biophysics, Vol. 433, Issue 1 https://doi.org/10.1016/j.abb.2004.08.017	journal	January 2005
The evolution of function within the Nudix homology clan: Function Evolution in the Nudix Homology Clan Srouji, John R.; Xu, Anting; Park, Annsea Proteins: Structure, Function, and Bioinformatics, Vol. 85, Issue 5 https://doi.org/10.1002/prot.25223	journal	March 2017
Bioconductor: open software development for computational biology and bioinformatics Gentleman, Robert C.; Carey, Vincent J.; Bates, Douglas M. Genome Biology, Vol. 5, Issue 10, p. R80 https://doi.org/10.1186/gb-2004-5-10-r80	journal	September 2004
Mutational analysis of a Dcp2-binding element reveals general enhancement of decapping by 5′-end stem-loop structures Li, You; Ho, Eric S.; Gunderson, Samuel I. Nucleic Acids Research, Vol. 37, Issue 7 https://doi.org/10.1093/nar/gkp087	journal	February 2009
Structural and functional control of the eukaryotic mRNA decapping machinery Arribas-Layton, Marcos; Wu, Donghui; Lykke-Andersen, Jens Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Vol. 1829, Issue 6-7 https://doi.org/10.1016/j.bbagrm.2012.12.006	journal	June 2013
New insights into decapping enzymes and selective mRNA decay: mRNA Decapping Enzymes in mRNA Decay Grudzien-Nogalska, Ewa; Kiledjian, Megerditch Wiley Interdisciplinary Reviews: RNA, Vol. 8, Issue 1 https://doi.org/10.1002/wrna.1379	journal	July 2016
Integration, scaling, space-group assignment and post-refinement Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144 https://doi.org/10.1107/S0907444909047374	journal	January 2010
Adenosine, NAD and FAD can initiate template-dependent RNA a synthesis catalyzed by Escherichia Coli RNA polymerase Malygin, A. G.; Shemyakin, M. F. FEBS Letters, Vol. 102, Issue 1 https://doi.org/10.1016/0014-5793(79)80926-6	journal	June 1979
Regulation of mRNA decapping Li, You; Kiledjian, Megerditch Wiley Interdisciplinary Reviews: RNA, Vol. 1, Issue 2 https://doi.org/10.1002/wrna.15	journal	May 2010
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Open Source Software for the Analysis of Microarray Data Dudoit, Sandrine; Gentleman, Robert C.; Quackenbush, John BioTechniques, Vol. 34, Issue 3S https://doi.org/10.2144/mar03dudoit	journal	March 2003
Glucose Restriction: Longevity SIRTainly, but without Building Muscle? Cantó, Carles; Auwerx, Johan Developmental Cell, Vol. 14, Issue 5 https://doi.org/10.1016/j.devcel.2008.04.012	journal	May 2008
Judge, Jury, and Executioner: DXO Functions as a Decapping Enzyme and Exoribonuclease in Pre-mRNA Quality Control Mugridge, Jeffrey S.; Gross, John D. Molecular Cell, Vol. 50, Issue 1 https://doi.org/10.1016/j.molcel.2013.03.025	journal	April 2013
Transcript-Specific Decapping and Regulated Stability by the Human Dcp2 Decapping Protein Li, Y.; Song, M. -G.; Kiledjian, M. Molecular and Cellular Biology, Vol. 28, Issue 3 https://doi.org/10.1128/mcb.01727-07	journal	November 2007
Bioconductor : open software development for computational biology and bioinformatics C., Gentleman, Robert; J., Carey, Vincent; M., Bates, Douglas BioMed Central https://doi.org/10.21256/zhaw-1907	text	January 2004

Cited By (2)

Structural studies of the eIF4E–VPg complex reveal a direct competition for capped RNA: Implications for translation Coutinho de Oliveira, Luciana; Volpon, Laurent; Rahardjo, Amanda K. Proceedings of the National Academy of Sciences, Vol. 116, Issue 48 https://doi.org/10.1073/pnas.1904752116	journal	November 2019
NAD Analogs in Aid of Chemical Biology and Medicinal Chemistry Depaix, Anais; Kowalska, Joanna Molecules, Vol. 24, Issue 22 https://doi.org/10.3390/molecules24224187	journal	November 2019

Similar Records

Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs

Journal Article · Wed May 20 00:00:00 EDT 2020 · Nucleic Acids Research · OSTI ID:1531008

Sharma, Sunny; Grudzien-Nogalska, Ewa; Hamilton, Keith; +4 more

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

Journal Article · Wed Mar 01 00:00:00 EST 2017 · Cell · OSTI ID:1531008

Jiao, Xinfu; Doamekpor, Selom K.; Bird, Jeremy G.; +4 more

A novel 5′-hydroxyl dinucleotide hydrolase activity for the DXO/Rai1 family of enzymes

Journal Article · Thu Nov 28 00:00:00 EST 2019 · Nucleic Acids Research · OSTI ID:1531008

Doamekpor, Selom K.; Gozdek, Agnieszka; Kwasnik, Aleksandra; +2 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Enzymes
RNA
X-ray crystallography

Title: Structural and mechanistic basis of mammalian Nudt12 RNA deNADding

Citation Formats

References (50)

Cited By (2)

Similar Records

Related Subjects