Nocturnin

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SpeciesHumanMouse
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Nocturnin is a human hydrolase enzyme that is involved in metabolism and its expression is controlled by the rhythmic circadian clock. It is encoded by the NOCT gene located on chromosome 4. Nocturnin contains a c-terminal structural domain of the Endonuclease/Exonuclease/phosphatase family.

The Drosophila melanogaster ortholog of Nocturnin is Curled. Knockouts of Curled lead to the curled wing phenotype in fruit flies. The curled wing phenotype was first discovered by Thomas Hunt Morgan in 1915.[1] In mice the Nocturnin ortholog is responsible for controlling diet and weight-gain, knockout mice do not gain weight when placed on a high-fat diet, when compared to normal mice containing Nocturnin.[2] In mice it has also been shown that Nocturnin is rhythmically expressed even when mice are placed in complete darkness, demonstrating that Nocturnin expression is driven by our body's internal clock.[3]

Enzymatic activity

Nocturnin was previously thought to deadenylate mRNAs of metabolic genes,[4] but two studies in 2018 demonstrated that Nocturnin does not directly posses ribonuclease activity.[5][6]

Structure

Nocturnin contains a c-terminal structural domain of the Endonuclease/Exonuclease/phosphatase family. Its fold is similar to that of DNase I, AP endonuclease, INPP5B, Sphingomyelin phosphodiesterase, TDP2, PDE12, and CNOT6L.

Five conserved catalytic residues help coordinate a Magnesium atom, which participates in the putative hydrolase reaction of Nocturnin.

References

  1. Gronke S, Bickmeyer I, Wunderlich R, Jackle H, Kuhnlein RP (2009). "curled Encodes the Drosophila Homolog of the Vertebrate Circadian Deadenylase Nocturnin". Genetics. 183 (1): 219–232. doi:10.1534/genetics.109.105601.
  2. Green CB, Douris N, Kojima S, Strayer CA, Fogerty J, Lourim D, Keller SR, Besharse JC (2007). "Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity". PNAS. 104 (23): 9, 888–93. doi:10.1073/pnas.0702448104. PMID 17517647.
  3. Wang Y, Osterbur DL, Megaw PL, Tosini G, Fukuhara C, Green CB, Besharse JC (2001). "Rhythmic expression of Nocturnin mRNA in multiple tissues of the mouse". BMC Developmental Biology. 1 (9). doi:10.1186/1471-213X-1-9. PMID 11394964.
  4. Baggs JE, Green CB (2003). "Nocturnin, a Deadenylase in Xenopus laevis Retina". Current Biology. 13 (3): 189–198. doi:10.1016/S0960-9822(03)00014-9.
  5. Estrella MA, Du J, Korennykh A (2018). "Crystal Structure of Human Nocturnin Catalytic Domain". Scientific Reports. 8 (1). doi:10.1038/s41598-018-34615-0. PMID 30389976.
  6. Abshire ET, Chasseur J, Bohn JA, Del Rizzo PA, Freddolino PL, Goldstrohm AC, Trievel RC (2018). "The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells". Nucleic Acids Research. 46 (12). doi:10.1093/nar/gky412.