Computational analysis of nascent peptides that induce ribosome stalling and their proteomic distribution in Saccharomyces cerevisiae

Interactions between the ribosomal exit tunnel and the nascent peptide can affect translation elongation rates. While previous studies have already demonstrated the feasibility of such interactions, little is known about the nature of the stalling peptide sequences and their distribution in the proteome. Here we ask which peptide sequences tend to occupy the tunnel of stalled ribosomes and how they are distributed in the proteome. Using computational analysis of ribosome profiling data from S. cerevisiae, we identified for the first time dozens of short stalling peptide sequences and studied their statistical properties. We found that short peptide sequences associated with ribosome stalling tend significantly to be either over-or underrepresented in the proteome. We then showed that the stalling interactions may occur at different positions along the length of the tunnel, prominently close to the P-site. Our findings throw light on the determinants of nascent peptide-mediated ribosome stalling during translation elongation and support the novel conjecture that mRNA translation affects the proteomic distribution of short peptide sequences.