ABSTRACT
Selenocysteine
is incorporated into proteins via “recoding” of UGA
from a stop codon to a sense codon, a process that requires specific
secondary structures in the 3′ untranslated region, termed
selenocysteine incorporation
sequence (SECIS) elements, and the protein factors that they
recruit. Whereas most selenoprotein mRNAs contain a single UGA codon
and a single SECIS element, selenoprotein P genes encode multiple UGAs
and two SECIS elements. We have identified evolutionary adaptations in
selenoprotein P genes that contribute to the efficiency of
incorporating multiple selenocysteine residues in this protein. The
first is a conserved, inefficiently decoded UGA codon in the N-terminal
region, which appears to serve both as a checkpoint for the presence of
factors required for selenocysteine incorporation and as a“
bottleneck,” slowing down the progress of elongating
ribosomes. The second adaptation involves the presence of introns
downstream of this inefficiently decoded UGA which confer the potential
for nonsense-mediated decay when factors required for selenocysteine
incorporation are limiting. Third, the two SECIS elements in
selenoprotein P mRNA function with differing efficiencies, affecting
both the rate and the efficiency of decoding different UGAs. The
implications for how these factors contribute to the decoding of
multiple selenocysteine residues are
discussed.