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Selenocysteine biosynthesis and mechanism of incorporation into growing proteins

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Abstract

The universal genetic code codes for the 20 canonical amino acids, while selenocysteine (Sec) is encoded by UGA, one of the three well-known stop codons. Selenocysteine is of particular interest of molecular biology, principally differing in the mechanism of incorporation into growing polypeptide chains from the other 20 amino acids. The process involves certain cis- and trans-active factors, such as the Sec insertion sequence (SECIS). The SECIS is in the 3′-untranslated mRNA region in eukaryotes and within the open reading frame located immediately downstream of the Sec UGA codon in bacteria, the difference leading to differences in the mechanism of Sec incorporation between the two domains of life. The trans-active factors include Sec-tRNA[Ser]Sec, which is synthesized by a unique system; the Sec-specific elongation factor EFsec; and a SECIS-binding protein (SBP2). Thus, many additional molecules are to be synthesized in the cell to allow Sec incorporation during translation. The fact makes Sec-containing proteins rather “expensive” and emphasizes their crucial role in metabolism.

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Abbreviations

Sec:

selenocysteine

SECIS:

selenocysteine insertion sequence

Sec-tRNA[Ser]Sec :

selenocysteine tRNA

SBP2:

SECIS-binding protein 2

EFsec:

elongation factor of selenocysteine

SelA:

prokaryotic selenocysteine synthase

SecS:

eukaryotic selenocysteine synthase

SPS1 and SPS2:

eukaryotic selenophosphate synthetases 1 and 2

SelD:

bacterial selenophosphate synthetase

SelB:

selenocysteine-specific elongation factor

PSTK:

O-phosphoseryl-tRN[Ser]Sec kinase

GPx1:

glutathione peroxidase 1

GPx4:

glutathione peroxidase 4

SID:

Sec incorporation domain

RBD:

RNA-binding domain

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Correspondence to E. G. Varlamova.

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Original Russian Text © E.G. Varlamova, M.V. Goltyaev, S.V. Novoselov, V.I. Novoselov, E.E. Fesenko, 2013, published in Molekulyarnaya Biologiya, 2013, Vol. 47, No. 4, pp. 558–567.

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Varlamova, E.G., Goltyaev, M.V., Novoselov, S.V. et al. Selenocysteine biosynthesis and mechanism of incorporation into growing proteins. Mol Biol 47, 488–495 (2013). https://doi.org/10.1134/S0026893313040134

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