부산대학교 도서관

A critical assumption of gene expression analysis is that mRNA abundances broadly correlate with protein abundance, but these two are often imperfectly correlated. Some of the discrepancy can be accounted for by two important mRNA features: codon usage and mRNA secondary structure. We present a new global factor, called mRNA:ncRNA avoidance, and provide evidence that avoidance increases translational efficiency. We also demonstrate a strong selection for the avoidance of stochastic mRNA:ncRNA interactions across prokaryotes, and that these have a greater impact on protein abundance than mRNA structure or codon usage. By generating synonymously variant green fluorescent protein (GFP) mRNAs with different potential for mRNA:ncRNA interactions, we demonstrate that GFP levels correlate well with interaction avoidance. Therefore, taking stochastic mRNA:ncRNA interactions into account enables precise modulation of protein abundance. DOI: http://dx.doi.org/10.7554/eLife.13479.001 eLife digest Many genes carry information for making proteins. To make a protein, a working copy of the information stored in DNA is first copied into a molecule of messenger RNA. These RNA messages are then interpreted by the ribosome, the molecular machine that makes proteins. Many messages are produced from each gene, and each message can be read multiple times. Thus, it should follow that the number of messages produced dictates the number of proteins made. However, this is not the case and the number of proteins produced cannot be completely predicted from knowing the number of messenger RNAs. Cells control how much of a given protein they produce through interactions between the messenger RNAs and other regulatory RNAs. The regulatory RNAs bind directly to a message and impede protein production. Because there are millions of RNAs in a cell, these interactions have evolved to be highly specific. Nevertheless, it seems inevitable that messenger RNAs would encounter other RNAs too, which could short-circuit gene regulation and lead to less protein being produced. Umu et al. have now asked if such short-circuit events are selected against during evolution. Computational tools were used to predict the strength of binding between the RNAs found in the dominant forms of microbial life on Earth: the bacteria and the archaea. This approach revealed that the majority of messenger RNAs bind more weakly to the most common RNA molecules found in cells than would be expected by chance. Weakened binding should prevent the RNA molecules from becoming tangled with each other and ensure that protein levels are not perturbed by unintended interactions between highly expressed messages and other RNAs. To test this hypothesis further, Umu et al. generated versions of the gene for a green fluorescent protein that differed only in how well their messenger RNAs could avoid interacting with the most abundant RNAs in E. coli cells. Those messengers that were designed to avoid interacting with other RNAs yielded far more protein than those that were not. The findings show that taking this kind of avoidance into account can improve predictions about how much protein will be produced and should therefore make it easier to control protein production in experimental systems. Finally, the messenger RNAs of some bacteria do not show such clear avoidance. However, these bacteria have a more complex internal cell structure. This finding hints at an alternative means for avoiding short-circuiting events that could be used by more complicated cells, such of those of animals and plants, which also contain much larger numbers of RNAs. DOI: http://dx.doi.org/10.7554/eLife.13479.002
Byline: Sinan Ugur Umu, Anthony M Poole, Renwick CJ Dobson, Paul P Gardner Introduction It should in principle be possible to predict protein abundance from genomic data. However, protein and [...]