Abstract
Thermodynamic descriptions are powerful tools to formally study complex gene expression programs evolved in living cells on the basis of macromolecular interactions. While transcriptional regulations are often modeled in the equilibrium, other interactions that occur in the cell follow a more complex pattern. Here, we adopt a nonequilibrium thermodynamic scheme to explain the RNA-RNA interaction underlying IS10 transposition. We determine the energy landscape associated with such an interaction at the base-pair resolution, and we present an original scaling law for expression prediction that depends on different free energies characterizing that landscape. Then, we show that massive experimental data of the IS10 RNA-controlled expression are better explained by this thermodynamic description in nonequilibrium. Overall, these results contribute to better comprehend the kinetics of post-transcriptional regulations and, more broadly, the functional consequences of processes out of the equilibrium in biology.
Highlights
Gene regulation is essential for the cell to adjust its physiology against environmental changes and persist
To resolve the energy landscape associated with the sRNAmRNA interaction with precision, the different gains and losses of free energy that occur as the reaction coordinate progresses need to be computed [Fig. 1(a)]
The different secondary structures that are progressively formed in that interaction range can be evaluated by hand according to a simplified physicochemical model with the stacking and looping free energies previously determined at 37 °C [21,22]
Summary
Gene regulation is essential for the cell to adjust its physiology against environmental changes and persist. Regulations based on RNA-RNA interactions are pervasive in biology Among other examples, they can be found within the mechanisms that bacteria exploit in response to stress, especially to regulate globally acting elements [5], that mammalian and plant cells employ to decoy functional RNAs [6], or that retroviruses follow to dimerize their genomes, such as in the case of the human immunodeficiency virus [7]. They can be found within the mechanisms that bacteria exploit in response to stress, especially to regulate globally acting elements [5], that mammalian and plant cells employ to decoy functional RNAs [6], or that retroviruses follow to dimerize their genomes, such as in the case of the human immunodeficiency virus [7] One such type of regulation consists in a small RNA (sRNA), naked or together with a protein, able to target a given messenger RNA (mRNA) to regulate its translation or stability [5]. The quantitative description of all these regulations that occur in vivo from simple, accurate, and formal mechanistic models is still a challenge
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