Operon mRNAs are organized into ORF-centric structures that predict translation efficiency

Abstract
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Abstract

Bacterial mRNAs are organized into operons consisting of discrete open reading frames (ORFs) in a single polycistronic mRNA. Individual ORFs on the mRNA are differentially translated, with rates varying as much as 100-fold. The signals controlling differential translation are poorly understood. Our genome-wide mRNA secondary structure analysis indicated that operonic mRNAs are comprised of ORF-wide units of secondary structure that vary across ORF boundaries such that adjacent ORFs on the same mRNA molecule are structurally distinct. ORF translation rate is strongly correlated with its mRNA structure in vivo, and correlation persists, albeit in a reduced form, with its structure when translation is inhibited and with that of in vitro refolded mRNA. These data suggests that intrinsic ORF mRNA structure encodes a rough blueprint for translation efficiency. This structure is then amplified by translation, in a self-reinforcing loop, to provide the structure that ultimately specifies the translation of each ORF.

Data availability

The following data sets were generated

1. Burkhardt DH
2. Rouskin S
3. Zhang Y
4. Li G
5. Weissman JS
6. Gross CA
(2016) Operon mRNAs are organized into ORF-centric structures that predict translation efficiency
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE77617).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77617

Article and author information

Author details

David H Burkhardt

Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Silvi Rouskin

Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Yan Zhang

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5440-1414
Gene-Wei Li

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
gwli@mit.edu

Competing interests
The authors declare that no competing interests exist.
Jonathan S Weissman

Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States

For correspondence
Jonathan.Weissman@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2445-670X
Carol A Gross

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States

For correspondence
cgrossucsf@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5595-9732

Funding

Howard Hughes Medical Institute

Jonathan S Weissman

National Institutes of Health

David H Burkhardt
Yan Zhang
Carol A Gross

Helen Hay Whitney Foundation

Gene-Wei Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.