The translation attenuating arginine-rich sequence in the extended signal peptide of the protein-tyrosine phosphatase PTPRJ/DEP1 is conserved in mammals

Abstract

The signal peptides, present at the N-terminus of many proteins, guide the proteins into cell membranes. In some proteins, the signal peptide contains an extended N-terminal region and a recessed hydrophobic signal sequence. Previously, it was demonstrated that the N-terminally extended signal peptide of the human PTPRJ contains a cluster of arginine residues, which attenuates translation. The analysis of the orthologous sequences revealed that this sequence is highly conserved among mammals. The PTPRJ transcripts in placentals, marsupials, and monotremes encode a stretch of 10 - 14 arginine residues, positioned 11-12 codons downstream of the initiating AUG. The remarkable conservation of the repeated arginine residues in the PTPRJ signal peptides points to their key role. Further, the presence of an arginine cluster in the extended signal peptides of other proteins (E3 ubiquitin-protein ligase, NOTCH3) is noted and indicates a more general importance of this cis-acting mechanism of translational suppression.