Correlations Among MRNA Secondary Structure, Gene Functions And Essentiality

RNA is one of the most important biological molecules. As the center media of geneticinformation, RNA play important roles in a series of biological processes, such as catalysis ofRNA splicing and processing, modification of pre-RNA, regulation of translation, degradationand localization of RNA and so on. There are a wide varity of RNAs, including mRNA, rRNA,tRNA and other non-coding RNAs. Among them, mRNA, rRNA and tRNA are responsiblefor biosynthesis of protein. Other non-coding RNAs are not transcriptional rubbish as intraditional concepts, and they often act as regulatory elements in the cell as well. For example,snRNA and snoRNA mainly involve RNA splicing and RNA modification, and the interactionbetween miRNA and target genes leads to gene silencing.Single-stranded RNAs with reverse complements can be folded into intricate secondarystructures which are closely related to their functions. Various secondary structures withinmRNAs often act as regulatory elements in a series of cellular processes, including translationinitiation, localization of mRNA or protein, translation elongation and protein folding, andhave important effects on translation efficiency and stability of mRNA. The mRNAsecondary structure participates in cellular processes in several ways. One possibility is thatthe secondary structure specifically interacts with RNA-binding factors, protein or smallmetabolites, with the structural specificity to regulate the downstream biological processes.Another way of regulation involve the local structural stability of mRNA. Numerous recentworks have focused on the discovery of these functional elements that contain the conservedmRNA structures. However, to date, regions with high structural stability have been largelyoverlooked. In this study, we investigated the high stability regions (HSRs) in the codingsequences (CDSs) of four enterobacteria and two non-enteric bacteria in a genome-wide scale,and mainly focused on the relationship between the number variation of secondary structureand gene functions.We used RNAfold in the Vienna RNA Secondary Structure Package to calculate theminimum folding free energy (MFE) along the CDSs sliding windows, and then surveyedhigh stability regions (HSRs) in CDSs based on the normalized folding free energy. The significantly higher HSR density in the native sequence than that in the control suggested aselective constraint on CDSs to maintain the high number of HSRs. In addition, the locationsof HSRs along CDSs were investigated as well. The result showed that a higher number ofHSRs were located in the5’ or3’ coding region compared with other regions. HSRs exhibiteda significantly higher degree of structural context robustness than the random, indicating adirect selective constraint on HSRs for high structural stability. A reduced ribosome speed wasdetected near the start position of HSR, implying a possibility that HSR acted as obstacle todrive translational pausing that coordinated protein synthesis. Interestingly, we found thatgenes with high HSR density were enriched in the processes of translation, protein folding,and cell division, whereas genes showing a lower value mainly involved in fermentation andbiosynthesis of biological molecules. In addition, essential genes exhibited higher HSRdensity than nonessential genes. We then verified that there was no significant correlationbetween HSR density and protein abundance, as well as between HSR density and mRNAhalf-life, indicating that the difference in HSR density among gene categories was notconnected with the variation in protein abundance and mRNA decay. Overall, our studypresented the previously unappreciated correlation between the number variation of HSRs andcellular processes.