Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis - Sorbonne Université Access content directly
Journal Articles Journal of Clinical Investigation Year : 2016

Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis

Abstract

Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome–encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2′-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis.
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hal-01295150 , version 1 (30-03-2016)

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Erik Schoenmakers, Bradley Carlson, Maura Agostini, Carla Moran, Odelia Rajanayagam, et al.. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. Journal of Clinical Investigation, 2016, 126 (3), pp.992-996. ⟨10.1172/JCI84747⟩. ⟨hal-01295150⟩
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