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Cell. 2018 Mar 22;173(1):181-195.e18. doi: 10.1016/j.cell.2018.02.034. Epub 2018 Mar 15.

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

Author information

1
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA. Electronic address: amustoe@unc.edu.
2
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
3
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA; Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
4
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
5
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA. Electronic address: weeks@unc.edu.

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.

KEYWORDS:

RNA binding proteins; RNA structure; non-coding RNA; ribosomal proteins; translation efficiency; translation regulation; translational coupling

Comment in

PMID:
29551268
PMCID:
PMC5866243
DOI:
10.1016/j.cell.2018.02.034
[Indexed for MEDLINE]
Free PMC Article

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