Number Variation of High Stability Regions Is Correlated with Gene Functions

Various regulatory elements in messenger RNAs (mRNAs) carrying the secondary structure play important roles in a wide range of expression processes. Numerous recent works have focused on the discovery of these functional elements that contain the conserved mRNA structures. However, to date, regions with high structural stability have been largely overlooked. In this study, we defined high stability regions (HSRs) in the coding sequences (CDSs) in bacteria based on the normalized folding free energy. We found that CDSs had high number of HSRs, and these HSRs showed high structural context robustness compared with random sequences, indicating a direct selective constraint imposed on HSRs. A reduced ribosome speed was detected near the start position of HSR, implying a possibility that HSR acted as obstacle to drive translational pausing that coordinated protein synthesis. Interestingly, we found that genes with high HSR density were enriched in the processes of translation, protein folding, and cell division. In addition, essential genes exhibited higher HSR density than nonessential genes. Overall, our study presented the previously unappreciated correlation between the number variation of HSRs and cellular processes.