Cell 173, 181–195 (2018)

The folding of RNA molecules into specific secondary structures is essential for their function in various biological processes. Current understanding of endogenous mRNA structure and its variation across genes is limited, and is mainly based on theoretical speculation and in vitro experiments using synthetic genes. Mustoe et al. used the selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) strategy to obtain high-resolution structure models for approximately 200 endogenous mRNAs in Escherichia coli. They found that individual mRNAs adopt diverse, complex structures and contain a large number of conserved regulatory motifs. In addition, the authors observed that the mRNA structure is unstable in the cellular environment, largely because of translation-mediated structural destabilization, and that the structure of ribosome-binding sites plays a primary role in determining translational efficiency. Finally, they found that gene-linking mRNA structures mediate translational coupling of adjacent genes in a polycistron. Overall, this high-resolution structural atlas of endogenous mRNA provides deeper understanding of the diversity, dynamics and function of mRNA structure, reveals new connections between RNA structure and translation and enables predictions of potential new RNA-regulatory structural elements.