title: Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate.
abstract: Translation of protein from mRNA is a complex multi-step process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.
authors.affiliation: DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands teg@mit.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Gorochowski
authors.affiliation: Department of Biochemistry, Institute of Biochemistry and Biology, University of Potsdam, 14476 Potsdam-Golm, Germany Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, 20146 Hamburg, Germany.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Ignatova
authors.affiliation: DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.affiliation: DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Roubos
mesh_terms: D003062:Codon / Q000235:genetics; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D009690:Nucleic Acid Conformation; D010441:Peptide Chain Elongation, Translational; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D003062:Codon; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer