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A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

ABSTRACT: Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.

SUBMITTER: Gu W

PROVIDER: S-EPMC2816680 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Gu Wanjun W Zhou Tong T Wilke Claus O CO

PLoS computational biology 20100205 2

Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evide ...[more]

PMID: 20140241

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Project description:BackgroundWithin the emerging field of synthetic biology, engineering paradigms have recently been used to design biological systems with novel functionalities. One of the essential challenges hampering the construction of such systems is the need to precisely optimize protein expression levels for robust operation. However, it is difficult to design mRNA sequences for expression at targeted protein levels, since even a few nucleotide modifications around the start codon may alter translational efficiency and dramatically (up to 250-fold) change protein expression. Previous studies have used ad hoc approaches (e.g., random mutagenesis) to obtain the desired translational efficiencies for mRNA sequences. Hence, the development of a mathematical methodology capable of estimating translational efficiency would greatly facilitate the future design of mRNA sequences aimed at yielding desired protein expression levels.ResultsWe herein propose a mathematical model that focuses on translation initiation, which is the rate-limiting step in translation. The model uses mRNA-folding dynamics and ribosome-binding dynamics to estimate translational efficiencies solely from mRNA sequence information. We confirmed the feasibility of our model using previously reported expression data on the MS2 coat protein. For further confirmation, we used our model to design 22 luxR mRNA sequences predicted to have diverse translation efficiencies ranging from 10-5 to 1. The expression levels of these sequences were measured in Escherichia coli and found to be highly correlated (R2 = 0.87) with their estimated translational efficiencies. Moreover, we used our computational method to successfully transform a low-expressing DsRed2 mRNA sequence into a high-expressing mRNA sequence by maximizing its translational efficiency through the modification of only eight nucleotides upstream of the start codon.ConclusionsWe herein describe a mathematical model that uses mRNA sequence information to estimate translational efficiency. This model could be used to design best-fit mRNA sequences having a desired protein expression level, thereby facilitating protein over-production in biotechnology or the protein expression-level optimization necessary for the construction of robust networks in synthetic biology.

Dataset Information

A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Publications

A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

Similar Datasets

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