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PMID: 29551268 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Cell ·Vol. 173 ·No. 1 ·2018-00-22 ·Pages 181-195.e18

Mustoe AM, Busan S, Rice GM, Hajdin CE, Peterson BK, Ruda VM, Kubica N, Nutiu R, Baryza JL, Weeks KM

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
MeSH Terms
Algorithms Binding Sites Cell-Free System DNA Primers/metabolism Electrophoretic Mobility Shift Assay Entropy Escherichia coli/genetics,metabolism Escherichia coli Proteins/chemistry,genetics,metabolism Models, Molecular Nucleic Acid Amplification Techniques/methods Nucleic Acid Conformation Protein Biosynthesis RNA Folding RNA, Messenger/chemistry,metabolism Recombinant Proteins/biosynthesis,chemistry,isolation & purification Ribosomes/chemistry,metabolism Untranslated Regions
Chemicals
DNA Primers Escherichia coli Proteins RNA, Messenger Recombinant Proteins Untranslated Regions
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Mustoe Anthony M
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA. Electronic address: amustoe@unc.edu.
Busan Steven
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Rice Greggory M
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA; Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Hajdin Christine E
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Peterson Brant K
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Ruda Vera M
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Kubica Neil
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Nutiu Razvan
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Baryza Jeremy L
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA.
Weeks Kevin M
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA. Electronic address: weeks@unc.edu.
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2018.02.034
Email
amustoe@unc.edu
weeks@unc.edu
Published
2018-00-22
Epub
2018-00-15
Pages
181-195.e18
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC5866243
Subset
IM
Grants
NIGMS NIH HHS · R35 GM122532 · United States
NCI NIH HHS · T32 CA009156 · United States
Corrections
CommentIn
PMID: 29662185
External Links
PubMed source DOI: 10.1016/j.cell.2018.02.034 PMC Full Text View journal details
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