- No free pool of Selenocysteine exists in the cell.
- Its high reactivity would incur damage to cells. Instead, cells store selenium in the less reactive selenide form (H2Se).
- Selenocysteine synthesis occurs on a specialized tRNA, which also functions to incorporate it into nascent polypeptides.
- The primary and secondary structure of Selenocysteine tRNA, tRNA(Sec), differ from those of standard tRNAs in several respects, most notably in having an 8-base (bacteria) or 10-base (eukaryotes) pair acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions.
- The Selenocysteine tRNAs are initially charged with serine by seryl-tRNA ligase, but the resulting Ser-tRNA(Sec) is not used for translation because it is not recognized by the normal translation factor (EF-Tu in bacteria, eEF1A in eukaryotes). Rather, the tRNA-bound seryl residue is converted to a selenocysteine-residue by the pyridoxal phosphate-containing enzyme selenocysteine synthase.
- Finally, the resulting Sec-tRNA(Sec) is specifically bound to an alternative translational elongation factor (SelB or mSelB (a.k.a. eEFSec)), which delivers it in a targeted manner to the ribosomes translating mRNAs for selenoproteins.
- The specificity of this delivery mechanism is brought about by the presence of an extra protein domain (in bacteria, SelB) or an extra subunit (SBP2 for eukaryotic mSelB/eEFSec) which bind to the corresponding RNA secondary structures formed by the SECIS elements in selenoprotein mRNAs.
There are more
than 20 human proteins that contain Selenocysteine.
where does Selenocysteine
comes from?
Selenocysteine
is not coded for directly in the genetic code. Instead, it is encoded in a
special way by a UGA codon, which is normally a stop codon. When cells are
grown in the absence of selenium, translation of selenoproteins terminates at
the UGA codon, resulting in a truncated, nonfunctional enzyme.
The UGA codon
is made to encode Selenocysteine by the presence of a SECIS
element (Selenocysteine Insertion Sequence) in the mRNA. The SECIS
element is defined by characteristic nucleotide sequences and secondary
structure base-pairing patterns. In bacteria, the SECIS element is located
immediately following the UGA codon within the reading frame for the
selenoproteins. In archaea and in eukaryotes, the SECIS element is in
the 3' untranslated region (3' UTR) of the mRNA, and can direct multiple
UGA codons to encode Selenocysteine residues.
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