title: Operon mRNAs are organized into ORF-centric structures that predict translation efficiency.
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.
authors.affiliation: Graduate Group in Biophysics, University of California, San Francisco, San Francisco, United States.|Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.|California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Burkhardt
authors.affiliation: California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.|Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.|Center for RNA Systems Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Silvi
authors.initials: S
authors.lastname: Rouskin
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.|Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Yan
authors.identifier: 0000-0001-5440-1414
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.|Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.|Center for RNA Systems Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Gene-Wei
authors.initials: GW
authors.lastname: Li
authors.affiliation: California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.|Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.|Center for RNA Systems Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Jonathan S
authors.identifier: 0000-0003-2445-670X
authors.initials: JS
authors.lastname: Weissman
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States.|California Institute of Quantitative Biology, University of California, San Francisco, San Francisco, United States.|Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Carol A
authors.identifier: 0000-0002-5595-9732
authors.initials: CA
authors.lastname: Gross
mesh_terms: D004926:Escherichia coli / Q000235:genetics*; D015870:Gene Expression; D023061:Gene Order; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D009876:Operon; D014176:Protein Biosynthesis; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger
keywords: DMS-seq; E. coli; codon usage; computational biology; infectious disease; mRNA secondary structure; microbiology; ribosome profiling; systems biology; translation efficiency