Amino Termini of Many Yeast Proteins Map to Downstream Start Codons

Comprehensive knowledge of proteome complexity is crucial
to understanding
cell function. Amino termini of yeast proteins were identified through
peptide mass spectrometry on glutaraldehyde-treated cell lysates as
well as a parallel assessment of publicly deposited spectra. An unexpectedly
large fraction of detected amino-terminal peptides (35%) mapped to
translation initiation at AUG codons downstream of the annotated start
codon. Many of the implicated genes have suboptimal sequence contexts
for translation initiation near their annotated AUG, and their ribosome
profiles show elevated tag densities consistent with translation initiation
at downstream AUGs as well as their annotated AUGs. These data suggest
that a significant fraction of the yeast proteome derives from initiation
at downstream AUGs, increasing significantly the repertoire of encoded
proteins and their potential functions and cellular localizations.