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Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing

Mustoe, Anthony M and Busan, Steven and Rice, Gregg and Hajdin, Christine and Peterson, Brant and Ruda, Vera and Kubica, Neil and Nutiu, Razvan and Baryza, Jeremy and Weeks, Kevin M (2018) Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing. Cell, 173 (1). pp. 181-195. ISSN 00928674

Abstract

mRNAs can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited our understanding of the prevalence and functions of mRNA structure. We use SHAPE-MaP experiments in living E. coli cells to derive quantitative, nucleotide-resolution structure models for 194 endogenous transcripts encompassing approximately 400 genes. Individual mRNAs have exceptionally diverse architectures, and most contain well-defined structures. Active translation destabilizes mRNA structure in cells. Nevertheless, mRNA structure remains similar between in-cell and cell-free environments, indicating broad potential for structure-mediated gene regulation. We find that the translation efficiency of endogenous genes is regulated by unfolding kinetics of structures overlapping the ribosome binding site. We discover conserved structured elements in 35% of UTRs, several of which we validate as novel protein binding motifs. RNA structure regulates every gene studied here in a meaningful way, implying that most functional structures remain to be discovered.

Item Type: Article
Date Deposited: 06 Apr 2018 00:45
Last Modified: 06 Apr 2018 00:45
URI: https://oak.novartis.com/id/eprint/34223

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