Regulation of Selenocysteine Incorporation into the Selenium Transport Protein, Selenoprotein P

Shetty, Sumangala P.; Shah, Rohan J.; Copeland, Paul R.

doi:10.1074/jbc.m114.590430

Cited by 49 publications

(50 citation statements)

References 55 publications

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“…Their data indicated that ribosomes that decoded one UGA as selenocysteine are more prone to decode another one. Another set of data from the group of Copeland performed in vitro, further confirms the processivity of UGA recoding (127). Interestingly, they find that other SECIS elements such as GPx4 support the processive insertion of selenocysteine, indicating an intrinsic property of the SECIS.…”

Section: The Ribosomessupporting

confidence: 53%

Update on Selenoprotein Biosynthesis

Bulteau

Chavatte

2015

Antioxidants & Redox Signaling

122

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The regulation of selenoproteins in response to a variety of pathophysiological conditions and cellular stressors, including selenium levels, oxidative stress, replicative senescence, or cancer, awaits further detailed investigation. Clearly, the efficiency of UGA-selenocysteine recoding is the limiting stage of selenoprotein synthesis. The sequence of events leading Sec-tRNA([Ser]Sec) delivery to ribosomal A site awaits further analysis, notably at the level of a three-dimensional structure.

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Section: The Ribosomessupporting

confidence: 53%

Update on Selenoprotein Biosynthesis

Bulteau

Chavatte

2015

Antioxidants & Redox Signaling

122

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“…This complex would channel efficient delivery of Sec into the ribosomal A -site thereby enhancing UGA readthrough (Small-Howard et al, 2006; Stapulionis and Deutscher, 1995). In fact, very recently selenium supplementation was demonstrated to enhance multiple but not single Sec incorporation events, further implicating a role for active aminoacylation and channeling of reactants (Shetty et al, 2014). Overall, therefore, it appears that the process of Sec incorporation is sufficient to prevent activation of the NMD pathway.…”

Section: 3 Interplay With Nonsense Mediated Decay (Nmd)mentioning

confidence: 99%

Selenocysteine incorporation: A trump card in the game of mRNA decay

Shetty

Copeland

2015

Biochimie

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The incorporation of the 21st amino acid, selenocysteine (Sec), occurs on mRNAs that harbor in-frame stop codons because the Sec-tRNASec recognizes a UGA codon. This sets up an intriguing interplay between translation elongation, translation termination and the complex machinery that marks mRNAs that contain premature termination codons for degradation, leading to nonsense mediated mRNA decay (NMD). In this review we discuss the intricate and complex relationship between this key quality control mechanism and the process of Sec incorporation in mammals.

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“…These findings raise additional exciting questions regarding the basic role of Sepp1 in transporting selenium to other organs, such as skeletal muscle and adipocytes, and the importance of this mechanism in energy homeostasis. One possible explanation for Sepp1 in Scly KO mice is that a truncated Sepp1 isoform is upregulated rather than a fulllength protein, as it is the case in selenium deficiency (15,57). Another possibility is that Sepp1 accumulates as a result of improper degradation due to Scly absence.…”

Section: Obesity In the Scly Ko Mousementioning

confidence: 99%

Diet-Induced Obesity in the Selenocysteine Lyase Knockout Mouse

Seale

Gilman

Hashimoto

et al. 2015

Antioxidants & Redox Signaling

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Aims: Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) seleniumadequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Involvement of selenoproteins in energy metabolism after Scly disruption was also examined in vitro in the murine hepatoma cell line, Hepa1-6, following palmitate treatment. Results: Scly KO mice were more susceptible to diet-induced obesity than their wild-type counterparts after feeding a high-fat selenium-adequate diet. Scly KO mice had aggravated hyperinsulinemia, hypercholesterolemia, glucose, and insulin intolerance, but unchanged inflammatory cytokines and expression of most selenoproteins, except increased serum selenoprotein P (Sepp1). Scly KO mice also exhibited enhanced hepatic levels of pyruvate and enzymes involved in the regulation of pyruvate cycling, such as pyruvate carboxylase (Pcx) and pyruvate dehydrogenase (Pdh). However, in vitro silencing of Scly in Hepa1-6 cells led to diminished Sepp1 expression, and concomitant palmitate treatment decreased Pdh expression. Innovation: The role of selenium in lipid metabolism is recognized, but specific selenium-dependent mechanisms leading to obesity are unclear. This study uncovers that Scly has a remarkable effect on obesity and metabolic syndrome development triggered by high-fat exposure, independent of the expression of most selenoproteins. Conclusion: Diet-induced obesity in Scly KO mice is aggravated, with effects on pyruvate levels and consequent activation of energy metabolism independent of selenoprotein levels. Antioxid. Redox Signal. 23, 761-774.

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Regulation of Selenocysteine Incorporation into the Selenium Transport Protein, Selenoprotein P

Cited by 49 publications

References 55 publications

Update on Selenoprotein Biosynthesis

Update on Selenoprotein Biosynthesis

Selenocysteine incorporation: A trump card in the game of mRNA decay

Diet-Induced Obesity in the Selenocysteine Lyase Knockout Mouse

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