The metabolites NADP+ and NADPH are the targets of the circadian protein Nocturnin (Curled)

Estrella, Michael A.; Du, Jin; Chen, Li; Rath, Sneha; Prangley, Eliza; Chitrakar, Alisha; Aoki, Tsutomu; Schedl, Paul; Rabinowitz, Joshua; Korennykh, Alexei

doi:10.1038/s41467-019-10125-z

Title: The metabolites NADP⁺ and NADPH are the targets of the circadian protein Nocturnin (Curled)

Journal Article · 29 May 2019 · Nature Communications

DOI: https://doi.org/10.1038/s41467-019-10125-z · OSTI ID:1624154

^[1];

^[2]; Chen, Li ^[3]; Rath, Sneha ^[2]; Prangley, Eliza ^[2]; Chitrakar, Alisha ^[2]; Aoki, Tsutomu ^[2]; Schedl, Paul ^[2]; Rabinowitz, Joshua ^[3]; Korennykh, Alexei ^[2]

Princeton Univ., NJ (United States). 216 Schultz Lab.; DOE/OSTI
Princeton Univ., NJ (United States). 216 Schultz Lab.
Princeton Univ., NJ (United States). 285 Frick Lab. and Lewis-Sigler Inst. for Integrative Genomics

Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP+ into NAD+ and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Å crystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2'-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Burroughs Wellcome Foundation; The Vallee Foundation; China Scholarship Council (CSC); Cancer Research UK—Lustgarten Foundation; National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0012704

OSTI ID:: 1624154

Alternate ID(s):: OSTI ID: 1688564

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (53)

Nocturnin, a Deadenylase in Xenopus laevis Retina Baggs, Julie E.; Green, Carla B. Current Biology, Vol. 13, Issue 3 https://doi.org/10.1016/S0960-9822(03)00014-9	journal	February 2003
Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity Wang, Hui; Morita, Masahiro; Yang, Xiuna The EMBO Journal, Vol. 29, Issue 15 https://doi.org/10.1038/emboj.2010.152	journal	July 2010
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins Calvo, Sarah E.; Clauser, Karl R.; Mootha, Vamsi K. Nucleic Acids Research, Vol. 44, Issue D1 https://doi.org/10.1093/nar/gkv1003	journal	October 2015
A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR- nuclear translocation N., Garg,; B., Green, C.; J., Rosen, C. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/msmm-7g89	text	January 2010
Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome Rath, Sneha; Donovan, Jesse; Whitney, Gena Proceedings of the National Academy of Sciences, Vol. 112, Issue 52 https://doi.org/10.1073/pnas.1513034112	journal	December 2015
The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice Niu, Shuang; Shingle, Danielle L.; Garbarino-Pico, Eduardo PLoS ONE, Vol. 6, Issue 11 https://doi.org/10.1371/journal.pone.0026954	journal	November 2011
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells Abshire, Elizabeth T.; Chasseur, Jennifer; Bohn, Jennifer A. Nucleic Acids Research, Vol. 46, Issue 12 https://doi.org/10.1093/nar/gky412	journal	June 2018
Systemic upregulation of NADPH oxidase in diet-induced obesity in rats Jiang, Fan; Lim, Han K.; Morris, Margaret J. Redox Report, Vol. 16, Issue 6 https://doi.org/10.1179/174329211x13049558293713	journal	November 2011
Correction: Curly Encodes Dual Oxidase, Which Acts with Heme Peroxidase Curly Su to Shape the Adult Drosophila Wing Hurd, Thomas Ryan; Liang, Feng-Xia; Lehmann, Ruth PLOS Genetics, Vol. 12, Issue 8 https://doi.org/10.1371/journal.pgen.1006285	journal	August 2016
A circadian-regulated gene, Nocturnin , promotes adipogenesis by stimulating PPAR-γ nuclear translocation Kawai, Masanobu; Green, Carla B.; Lecka-Czernik, Beata Proceedings of the National Academy of Sciences, Vol. 107, Issue 23 https://doi.org/10.1073/pnas.1000788107	journal	May 2010
Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity Green, C. B.; Douris, N.; Kojima, S. Proceedings of the National Academy of Sciences, Vol. 104, Issue 23 https://doi.org/10.1073/pnas.0702448104	journal	May 2007
The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors Wood, Edgar R.; Bledsoe, Randy; Chai, Jing Journal of Biological Chemistry, Vol. 290, Issue 32 https://doi.org/10.1074/jbc.M115.653113	journal	June 2015
Crystal Structure of Human Nocturnin Catalytic Domain Estrella, Michael A.; Du, Jin; Korennykh, Alexei Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-34615-0	journal	November 2018
Maturation of selected human mitochondrial tRNAs requires deadenylation Pearce, Sarah F.; Rorbach, Joanna; Haute, Lindsey Van eLife, Vol. 6 https://doi.org/10.7554/eLife.27596	journal	July 2017
NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus Cantó, Carles; Menzies, Keir J.; Auwerx, Johan Cell Metabolism, Vol. 22, Issue 1 https://doi.org/10.1016/j.cmet.2015.05.023	journal	July 2015
NAD+ Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus Cantó, Carles; Menzies, Keir J.; Auwerx, Johan Cell Metabolism, Vol. 22, Issue 1 https://doi.org/10.1016/j.cmet.2015.05.023	journal	July 2015
curled Encodes the Drosophila Homolog of the Vertebrate Circadian Deadenylase Nocturnin Grönke, Sebastian; Bickmeyer, Iris; Wunderlich, Roman Genetics, Vol. 183, Issue 1 https://doi.org/10.1534/genetics.109.105601	journal	July 2009
Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity Li, Y.; Mouche, S.; Sajic, T. International Journal of Obesity, Vol. 36, Issue 12 https://doi.org/10.1038/ijo.2011.279	journal	March 2012
curled Encodes the Drosophila Homolog of the Vertebrate Circadian Deadenylase Nocturnin Grönke, Sebastian; Bickmeyer, Iris; Wunderlich, Roman Genetics, Vol. 183, Issue 1 https://doi.org/10.1534/genetics.109.105601	journal	July 2009
Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity Wang, Hui; Morita, Masahiro; Yang, Xiuna The EMBO Journal, Vol. 29, Issue 15 https://doi.org/10.1038/emboj.2010.152	journal	July 2010
The role of phosphodiesterase 12 (PDE12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors Edgar, Wood,; Bruce, Wisely,; Sarah, Harris-Gurley, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mvmy-zp88	text	January 2015
Mir34a constrains pancreatic carcinogenesis Hidalgo-Sastre, Ana; Lubeseder-Martellato, Clara; Engleitner, Thomas Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-66561-1	journal	June 2020
Temporal Control of Metabolic Amplitude by Nocturnin Stubblefield, Jeremy J.; Gao, Peng; Kilaru, Gokhul Cell Reports, Vol. 22, Issue 5 https://doi.org/10.1016/j.celrep.2018.01.011	journal	January 2018
Deficiency in the NADPH oxidase 4 predisposes towards diet-induced obesity Li, Y.; Mouche, S.; Sajic, T. International Journal of Obesity, Vol. 36, Issue 12 https://doi.org/10.1038/ijo.2011.279	journal	March 2012
The role of phosphodiesterase 12 (PDE12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors Edgar, Wood,; Bruce, Wisely,; Sarah, Harris-Gurley, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mvmy-zp88	text	January 2015
Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L Chitrakar, Alisha; Rath, Sneha; Donovan, Jesse Proceedings of the National Academy of Sciences, Vol. 116, Issue 6 https://doi.org/10.1073/pnas.1818363116	journal	January 2019
NADPH-dependent beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms. Smeland, T. E.; Nada, M.; Cuebas, D. Proceedings of the National Academy of Sciences, Vol. 89, Issue 15 https://doi.org/10.1073/pnas.89.15.6673	journal	August 1992
Curly Encodes Dual Oxidase, Which Acts with Heme Peroxidase Curly Su to Shape the Adult Drosophila Wing Hurd, Thomas Ryan; Liang, Feng-Xia; Lehmann, Ruth PLOS Genetics, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pgen.1005625	journal	November 2015
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins Calvo, Sarah E.; Clauser, Karl R.; Mootha, Vamsi K. Nucleic Acids Research, Vol. 44, Issue D1 https://doi.org/10.1093/nar/gkv1003	journal	October 2015
A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection Jean Beltran, Pierre M.; Mathias, Rommel A.; Cristea, Ileana M. Cell Systems, Vol. 3, Issue 4 https://doi.org/10.1016/j.cels.2016.08.012	journal	October 2016
Maturation of selected human mitochondrial tRNAs requires deadenylation Pearce, Sf; Rorbach, J.; Van Haute, Lindsey Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.13385	text	January 2017
Systemic upregulation of NADPH oxidase in diet-induced obesity in rats Jiang, Fan; Lim, Han K.; Morris, Margaret J. Redox Report, Vol. 16, Issue 6 https://doi.org/10.1179/174329211X13049558293713	journal	November 2011
Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin Green, C. B.; Besharse, J. C. Proceedings of the National Academy of Sciences, Vol. 93, Issue 25 https://doi.org/10.1073/pnas.93.25.14884	journal	December 1996
Temporal Control of Metabolic Amplitude by Nocturnin Stubblefield, Jeremy J.; Gao, Peng; Kilaru, Gokhul Cell Reports, Vol. 22, Issue 5 https://doi.org/10.1016/j.celrep.2018.01.011	journal	January 2018
The dawn Phenomenon Revisited: Implications for Diabetes Therapy Carroll, Mary F.; Schade, David S. Endocrine Practice, Vol. 11, Issue 1 https://doi.org/10.4158/EP.11.1.55	journal	January 2005
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Nocturnin: at the crossroads of clocks and metabolism Stubblefield, Jeremy J.; Terrien, Jérémy; Green, Carla B. Trends in Endocrinology & Metabolism, Vol. 23, Issue 7 https://doi.org/10.1016/j.tem.2012.03.007	journal	July 2012
Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L Chitrakar, Alisha; Rath, Sneha; Donovan, Jesse Proceedings of the National Academy of Sciences, Vol. 116, Issue 6 https://doi.org/10.1073/pnas.1818363116	journal	January 2019
Identification and characterization of a human mitochondrial NAD kinase Ohashi, Kazuto; Kawai, Shigeyuki; Murata, Kousaku Nature Communications, Vol. 3, Issue 1 https://doi.org/10.1038/ncomms2262	journal	January 2012
Maturation of selected human mitochondrial tRNAs requires deadenylation Pearce, Sarah F.; Rorbach, Joanna; Haute, Lindsey Van eLife, Vol. 6 https://doi.org/10.7554/elife.27596	journal	July 2017
Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin Green, C. B.; Besharse, J. C. Proceedings of the National Academy of Sciences, Vol. 93, Issue 25 https://doi.org/10.1073/pnas.93.25.14884	journal	December 1996
ExPASy: the proteomics server for in-depth protein knowledge and analysis Gasteiger, E. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg563	journal	July 2003
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells Abshire, Elizabeth T.; Chasseur, Jennifer; Bohn, Jennifer A. Nucleic Acids Research, Vol. 46, Issue 12 https://doi.org/10.1093/nar/gky412	journal	June 2018
Crystal Structure of Human Nocturnin Catalytic Domain Estrella, Michael A.; Du, Jin; Korennykh, Alexei Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-34615-0	journal	November 2018
Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity Green, C. B.; Douris, N.; Kojima, S. Proceedings of the National Academy of Sciences, Vol. 104, Issue 23 https://doi.org/10.1073/pnas.0702448104	journal	May 2007
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
Curly Encodes Dual Oxidase, Which Acts with Heme Peroxidase Curly Su to Shape the Adult Drosophila Wing Hurd, Thomas Ryan; Liang, Feng-Xia; Lehmann, Ruth PLOS Genetics, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pgen.1005625	journal	November 2015
An integrative analysis of the age-associated multi-omic landscape across cancers Chatsirisupachai, Kasit; Lesluyes, Tom; Paraoan, Luminita Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-22560-y	journal	April 2021
A Portrait of the Human Organelle Proteome In Space and Time during Cytomegalovirus Infection Jean Beltran, Pierre M.; Mathias, Rommel A.; Cristea, Ileana M. Cell Systems, Vol. 3, Issue 4 https://doi.org/10.1016/j.cels.2016.08.012	journal	October 2016
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles Subramanian, A.; Tamayo, P.; Mootha, V. K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550 https://doi.org/10.1073/pnas.0506580102	journal	September 2005
MitoFates: Improved Prediction of Mitochondrial Targeting Sequences and Their Cleavage Sites Fukasawa, Yoshinori; Tsuji, Junko; Fu, Szu-Chin Molecular & Cellular Proteomics, Vol. 14, Issue 4 https://doi.org/10.1074/mcp.M114.043083	journal	February 2015
Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome Rath, Sneha; Donovan, Jesse; Whitney, Gena Proceedings of the National Academy of Sciences, Vol. 112, Issue 52 https://doi.org/10.1073/pnas.1513034112	journal	December 2015
Coordination of circadian timing in mammals Reppert, Steven M.; Weaver, David R. Nature, Vol. 418, Issue 6901 https://doi.org/10.1038/nature00965	journal	August 2002

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Title: The metabolites NADP+ and NADPH are the targets of the circadian protein Nocturnin (Curled)

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Title: The metabolites NADP⁺ and NADPH are the targets of the circadian protein Nocturnin (Curled)