A comparative genomics study on the effect of individual amino acids on ribosome stalling.

Renana Sabi,Tamir Tuller

doi:10.1186/1471-2164-16-s10-s5

Abstract

BackgroundDuring protein synthesis, the nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel. Biochemical interactions between the nascent peptide and the tunnel may stall the ribosome movement and thus affect the expression level of the protein being synthesized. Earlier studies focused on one model organism (S. cerevisiae), have suggested that certain amino acid sequences may be responsible for ribosome stalling; however, the stalling effect at the individual amino acid level across many organisms has not yet been quantified.ResultsBy analyzing multiple ribosome profiling datasets from different organisms (including prokaryotes and eukaryotes), we report for the first time the organism-specific amino acids that significantly lead to ribosome stalling. We show that the identity of the stalling amino acids vary across the tree of life. In agreement with previous studies, we observed a remarkable stalling signal of proline and arginine in S. cerevisiae. In addition, our analysis supports the conjecture that the stalling effect of positively charged amino acids is not universal and that in certain conditions, negative charge may also induce ribosome stalling. Finally, we show that the beginning part of the tunnel tends to undergo more interactions with the translated amino acids than other positions along the tunnel.ConclusionsThe reported results support the conjecture that the ribosomal exit tunnel interacts with various amino acids and that the nature of these interactions varies among different organisms. Our findings should contribute towards better understanding of transcript and proteomic evolution and translation elongation regulation.

Highlights

IntroductionThe nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel
During protein synthesis, the nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel
Ribosome profiling experiments include the following major stages (Figure 1A): cells are treated with cycloheximide to arrest translating ribosomes; RNA fragments protected by ribosomes from RNases are isolated and processed for high-throughput sequencing, resulting in reads of ribosomes protected footprints

Summary

Introduction

The nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel. Biochemical interactions between the nascent peptide and the tunnel may stall the ribosome movement and affect the expression level of the protein being synthesized. Translation elongation is an iterative stage of translation in which the ribosome scans the mRNA sequence and decodes it into a specific protein by adding one amino acid at the time to the growing peptide chain. It has been suggested that the speed by which ribosomes progress along the mRNA is affected by different local features of the coding sequence. The overall electrostatic potential of the RET is negative and varies in magnitude along the tunnel [19,20,21,22,23]; it was suggested that a nascent peptide that contains charged amino acids may undergo electrostatic interaction with the exit tunnel [19]. The expansion in diameter enables the partial folding of the translated peptide [28], the cramped dimensions of the tunnel prohibit a folding of whole protein domains and only tertiary/secondary structures of small segments are allowed [29]

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Discussion

Conclusion