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Elife. 2017 Jan 31;6. pii: e22037. doi: 10.7554/eLife.22037.

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

Burkhardt DH1,2,3, Rouskin S3,4,5, Zhang Y2,6, Li GW3,4,5, Weissman JS3,4,5, Gross CA2,3,6.

Author information

1
Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States.
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.
3
California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.
4
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
5
Center for RNA Systems Biology, University of California, San Francisco, San Francisco, United States.
6
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States.

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 suggest 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.

KEYWORDS:

DMS-seq; E. coli; codon usage; computational biology; infectious disease; mRNA secondary structure; microbiology; ribosome profiling; systems biology; translation efficiency

PMID:
28139975
PMCID:
PMC5318159
DOI:
10.7554/eLife.22037
[Indexed for MEDLINE]
Free PMC Article

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