Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesisReport as inadecuate


Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis


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Publication Date: 2016-02-08

Journal Title: Journal of Clinical Investigation

Publisher: American Society for Clinical Investigation

Volume: 126

Issue: 3

Pages: 992-996

Type: Article

Metadata: Show full item record

Citation: Schoenmakers, E., Carlson, B., Agostini, M., Moran, C., Rajanayagam, O., Bochukova, E., Tobe, R., et al. (2016). Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. Journal of Clinical Investigation, 126 (3), 992-996.

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Abstract: Selenium, a trace element essential for human health, is incorporated into more than 25 human selenocysteine-containing (Sec) proteins, via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA (tRNA[Ser]Sec). We report the first human tRNA[Ser]Sec mutation, with markedly reduced expression of stress-related but not housekeeping selenoproteins. This deficit, likely mediated by reduced expression and diminished 2’-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec, is restored by cellular complementation with normal tRNA[Ser]Sec, demonstrating the importance of such tRNA modification for normal selenoprotein synthesis.

Sponsorship: Our research is supported by funding from the Wellcome Trust (100585/Z/12/Z to NS, 095564/Z/11/Z to KC), the National Institute for Health Research Biomedical Research Centre Cambridge (CM, NS, KC) or Great Ormond Street (FM) and Intramural Research Program of the Center for Cancer Research, NCI, NIH (DLH).

Identifiers:

This record's URL: http://dx.doi.org/10.1172/JCI84747https://www.repository.cam.ac.uk/handle/1810/254664





Author: Schoenmakers, ErikCarlson, BradleyAgostini, MauraMoran, CarlaRajanayagam, OdeliaBochukova, ElenaTobe, RyutaPeat, RachelGevers, Eve

Source: https://www.repository.cam.ac.uk/handle/1810/254664



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