Selecting against accidental

T ranslation is the process by which the genetic information in a molecule of messenger RNA (mRNA) produces a protein, and the rate at which protein is produced from a given mRNA molecule is called the translation efficiency. This number is different for different mRNA molecules (Maier et al., 2009; Guo et al., 2008), which is why researchers are trying to determine which features of these molecules affect their translation efficiency (Tuller et al., 2010; Ferreira et al., 2013; Kozak, 2005; Gingold and Pilpel, 2011). Now, in eLife, Paul Gardner of the University of Canterbury and colleagues – including Sinan Umu (as first author), Anthony Poole and Renwick Dobson – report that the translation efficiency in bacteria and archaea is influenced by a phenomenon called "avoidance" (Umu et al., 2016). Avoidance is the degree to which an mRNA molecule avoids random interactions with noncoding RNA molecules in the cell. Noncoding RNAs, as their name suggests, do not code for proteins, but they still make up a majority of the RNA in any given cell. Indeed, the researchers show that the levels of noncoding RNAs in bacterial cells are two orders of magnitude greater than the levels of mRNAs. To estimate the probability of random basepairing interactions taking place between mRNAs and noncoding RNAs, consider a fivebase region in a single mRNA. This region can have any one of a possible 4^5=1024 sequences. If the total number of bases from all the noncoding RNAs in the cell is S, then the number of noncoding RNAs in the cell that have a perfectly complementary five-base region is approximately S/1024. Umu et al. studied 325 noncoding RNAs so, assuming an average length of 200 bases for these, we have S » 325*200 » 65000. Therefore, on average, the number of these noncoding RNAs that have a five-base region that is perfectly complementary to the five-base region in the mRNA will be 65000/1024 » 63. Given the number of mRNAs and noncoding RNAs that are found in cells, random interactions between the two are inevitable. However, if we find that a given mRNA has base-pairing interactions with fewer noncoding RNAs than expected, then this is avoidance (Figure 1A). Realistically, RNA binding interactions are governed by thermodynamics and do not always follow strict pairing rules. Furthermore, RNA molecules can pair with themselves in intramolecular interactions and must “unfold” a given region in order to pair with another molecule. Thus it is important to quantify mRNA-noncoding RNA interactions with net "binding energy" calculations. The binding energy quantifies the thermodynamics of RNA base-pairing, with low binding energies indicating very stable interactions. To explore the phenomenon of avoidance, Umu et al. used a computational Copyright Corley and Laederach. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Related research article Umu SU, Poole