![]() ( C) A detailed view of the active site of the 2.41 Å resolution structure. ( B) Cartoon representation of the NOCT 120–431 1.48 Å resolution structure denoting the secondary structural elements of the NOCT catalytic domain colored using the PyMOL chainbow settings. ( A) A cartoon representation of the 1.48 Å resolution structure of the NOCT catalytic domain (residues 120–431). The crystal structure of NOCT reveals a conserved structure, active site and basic cleft. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development. ![]() We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3' end of the mRNA, as reporters terminating with a 3' MALAT1 structure cannot be repressed by NOCT. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. ![]() Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. ![]() However, the mechanisms by which NOCT regulates these processes remain to be determined. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. This work also includes the first comprehensive account of the critical response to his writing while underscoring the way the much-altered English adaptation from 1970 shaped that response.Ī momentous achievement that situates a new classic in the twenty-first century, Hunter with Harpoon brings readers back to the roots of Markoosie Patsauq's Inuit story to experience it as it was originally written.The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. This critical edition, complete with the story in both Inuktitut syllabics and Latin script, utilizes the author's handwritten manuscript as well as interviews with Patsauq to produce a new, rigorous examination of this literary and cultural milestone. In collaboration with Patsauq, Valerie Henitiuk and Marc-Antoine Mahieu have foregrounded the original Inuktitut text to inform their translations into both English and French. In the years that followed the widely acclaimed English edition was translated into many different languages, but what has remained obscured until the present day is the Inuktitut text originally produced by the author. ![]() Published in English under the title Harpoon of the Hunter in 1970 by McGill-Queen's University Press, that version of the story was Patsauq's own adaptation. Fifty years ago, Markoosie Patsauq, then a bush pilot in his late twenties living in the tiny, isolated High Arctic community of Resolute, spent his spare time quietly writing a story that effectively emerged as the first Indigenous novel released in Canada. ![]()
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