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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Mar 20

PMID 29551268

Citations 138

Authors

Anthony M Mustoe

Steven Busan

Greggory M Rice

Christine E Hajdin

Brant K Peterson

Vera M Ruda

Neil Kubica

Razvan Nutiu

Jeremy L Baryza

Kevin M Weeks

Affiliations

Soon will be listed here.

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.

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