Translation is a major determinant of mRNA secondary structures in mammalian cells

mRNA has dynamic structures in vivo. Whether these mRNA structural changes are the cause or the effects of gene expression dynamics under various biological processes, however, is largely unknown in mammalian cells. Here we studied the relationship between mRNA secondary structures and mRNA translation in the macrophage-mediated inflammatory response. Using dimethyl sulfate (DMS) mutational profiling with sequencing, we probed global mRNA secondary structural dynamics during this biological process. We found that although there is a strong correlation between mRNA accessibility, determined by RNA's reactivity to DMS, and translation efficiency at steady states, the changes of mRNA accessibility do not correlate with the changes of mRNA translation efficiency during the inflammatory response. Interestingly, global mRNA accessibility displays an evolutionally conserved 3-nucleotide periodicity in the coding region, and the intensity of this periodicity correlates with translation efficiency. Altogether, our results indicate that mRNA accessibility dynamics are not the cause of alterations of mRNA translation, and mRNA translation is a major determinant of mRNA secondary structures in mammalian cells.