{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNocturnin (NOCT) is a circadian clock–controlled gene whose transcription oscillates in a robust and time‐dependent manner. In human cells, the nocturnin promoter is activated by the CLOCK/BMAL1 heterodimer via E‐box elements, thereby linking the core circadian machinery to the regulation of downstream cellular processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have further implicated NOCT (also known as CCRN4L) in metabolic homeostasis and cancer risk. Variations in the NOCT gene have been associated with differences in body mass index and predisposition to non–small cell lung cancer, indicating that NOCT may serve as a critical nexus between nutrient absorption, metabolic regulation, and circadian timing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, NOCT functions as an exoribonuclease with similarities to the CCR4-class deadenylases. Structural studies of its catalytic domain reveal that NOCT conserves key catalytic residues reminiscent of other exoribonucleases, yet its surface properties and an unusually narrow active site pocket differentiate it from its classical deadenylase counterparts. Although NOCT can reduce the abundance and translation of target mRNAs in cells, purified recombinant NOCT shows little in vitro ribonuclease activity, suggesting that additional factors or regulatory modifications may be required for its full enzymatic function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in mRNA turnover, NOCT exhibits cell type–specific expression and differential subcellular localization—including cytoplasmic and mitochondrial distributions—that enable it to influence a variety of physiological processes. Its actions affect not only the stability of mRNAs related to metabolic enzymes but also modulate intracellular NAD(H) and NADP(H) levels, thereby contributing to lipid metabolism, bone development, and neuronal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ran Li, Jiping Yue, Yu Zhang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in the NOC gene is associated with body mass index in Chinese subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0069622"}], "href": "https://doi.org/10.1371/journal.pone.0069622"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23922759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23922759"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Patricia Couto, Debora Miranda, Renalice Vieira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between CLOCK, PER3 and CCRN4L with non‑small cell lung cancer in Brazilian patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2014.2224"}], "href": "https://doi.org/10.3892/mmr.2014.2224"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24821610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24821610"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elizabeth T Abshire, Jennifer Chasseur, Jennifer A Bohn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gky412"}], "href": "https://doi.org/10.1093/nar/gky412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29860338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29860338"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kelsey L Hughes, Elizabeth T Abshire, Aaron C Goldstrohm "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2018.1526541"}], "href": "https://doi.org/10.1080/15476286.2018.1526541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30257600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30257600"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Michael A Estrella, Jin Du, Alexei Korennykh "}, {"type": "b", "children": [{"type": "t", "text": "Crystal Structure of Human Nocturnin Catalytic Domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-34615-0"}], "href": "https://doi.org/10.1038/s41598-018-34615-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30389976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30389976"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Massimo Bracci, Alfredo Copertaro, Veronica Ciarapica, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NOCTURNIN"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Gene Diurnal Variation in Healthy Volunteers and Expression Levels in Shift Workers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2019/7582734"}], "href": "https://doi.org/10.1155/2019/7582734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31467910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31467910"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elizabeth T Abshire, Kelsey L Hughes, Rucheng Diao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.012618"}], "href": "https://doi.org/10.1074/jbc.RA120.012618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32839274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32839274"}]}]}]}