Composite effects of gene determinants on the translation speed and density of ribosomes

Tuller Tamir, Veksler-Lublinsky Isana, Gazit Nir, Kupiec Martin, Ruppin Eytan, Ziv-Ukelson, Ziv-Ukelson Michal

Description

Translation is a central process of life, and its regulation is crucial for cell growth. In this article, focusing on two model organisms, Escherichia coli and Saccharomyces cerevisiae , we study how three major local features of a gene's coding sequence (its adaptation to the tRNA pool, its amino acid charge, and its mRNA folding energy) affect its translation elongation. Results We find that each of these three different features has a non-negligible distinct correlation with the speed of translation elongation. In addition, each of these features might contribute independently to slowing down ribosomal speed at the beginning of genes, which was suggested in previous studies to improve ribosomal allocation and the cost of translation, and to decrease ribosomal jamming. Remarkably, a model of ribosomal translation based on these three basic features highly correlated with the genomic profile of ribosomal density. The robustness to transcription errors in terms of the values of these features is higher at the beginnings of genes, suggesting that this region is important for translation. Conclusions The reported results support the conjecture that translation elongation speed is affected by the three coding sequence determinants mentioned above, and not only by adaptation to the tRNA pool; thus, evolution shapes all these determinants along the coding sequences and across genes to improve the organism's translation efficiency.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 5
• Langue: English
• Poids de l'ouvrage: 9 Mo

Extrait

Tuller et al . Genome Biology 2011, 12 :R110 http://genomebiology.com/2011/12/11/R110

R E S E A R C H Open Access Composite effects of gene determinants on the translation speed and density of ribosomes Tamir Tuller 1* † , Isana Veksler-Lublinsky 2 † , Nir Gazit 3 , Martin Kupiec 4 , Eytan Ruppin 3,5 and Michal Ziv-Ukelson 2

Abstract Background: Translation is a central process of life, and its regulation is crucial for cell growth. In this article, focusing on two model organisms, Escherichia coli and Saccharomyces cerevisiae , we study how three major local features of a gene ’ s coding sequence (its adaptation to the tRNA pool, its amino acid charge, and its mRNA folding energy) affect its translation elongation. Results: We find that each of these three different features has a non-negligible distinct correlation with the speed of translation elongation. In addition, each of these features might contribute independently to slowing down ribosomal speed at the beginning of genes, which was suggested in previous studies to improve ribosomal allocation and the cost of translation, and to decrease ribosomal jamming. Remarkably, a model of ribosomal translation based on these three basic features highly correlated with the genomic profile of ribosomal density. The robustness to transcription errors in terms of the values of these features is higher at the beginnings of genes, suggesting that this region is important for translation. Conclusions: The reported results support the conjecture that translation elongation speed is affected by the three coding sequence determinants mentioned above, and not only by adaptation to the tRNA pool; thus, evolution shapes all these determinants along the coding sequences and across genes to improve the organism ’ s translation efficiency.

Background controlled by the codon order in the coding sequence Gene translation is a central biological process in all liv-  [8,17]. This is partially achieved by a ‘ ramp ’ at the begin- ing organisms by which an mRNA sequence is decoded  ning of the coding sequences composed of less efficient by the ribosome to synthesize a specific protein. During codons. This ramp slows down ribosomal speed, and the elongation stage of this process, each codon is itera-  thus improves their allocation and minimizes the number tively translated by the ribosome to an amino acid. of collisions between them. In addition, it was shown that Translation elongation is k nown to be conserved in all there is global selection for weak mRNA folding at the living organisms (Bacteria, Archaea, and eukaryotes [1]);  beginning of the coding sequence to improve the binding thus, understanding this process and the determinants of ribosomes [7,8,14,16,17,21, 22]. Furthermore, recent, related to it have important ramifications for human  small-scale studies also suggested that positively charged health [2-4], biotechnology [5-10], and evolution  amino acids slow down ribosomes as the electrostatic [4,8,11]. potential inside the exit tunnel is negative [23,24]. Finally, Indeed, gene translation has been the topic of an based on large scale measurements of ribosome densities increasing number of studies in recent years (see, for  [13,15] it has been demonstrated that the density (and example, [5,7,8,12-20]). Specifically, it was recently dis- thus the speed [8]) of ribosomes varies within a gene and covered that the efficiency of translation can be  across genes. We have previously shown that the speed and alloca- cted b * † C C o o rrespondence:[e-mail] t o i f o t n h o e f a ri d b a o p s t o at m i e o s n in of g c e o ne d s o i n s s a a ff l e ongthe y m th t e o di t s h tr e ib t u R ti N o A n 1 Dep n ar t t ri m bu e t n e t d of eq Bi u o al m ly edicalEngineering,FacultyofEngineering,TelAviv pool of the organism [8]. The goal of this paper is to F U u n ll iv li e s r t sit o y f , a R u a th m o a r t i A n v f i o v r 6 m 9 a 9 ti 7 o 8 n ,I i s s ra a e v l ailableattheendofthearticle study how the different features of coding sequences © 2011 Tuller et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.