title: Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation.
abstract: Ribosome-footprint profiling provides genome-wide snapshots of translation, but technical challenges can confound its analysis. Here, we use improved methods to obtain ribosome-footprint profiles and mRNA abundances that more faithfully reflect gene expression in Saccharomyces cerevisiae. Our results support proposals that both the beginning of coding regions and codons matching rare tRNAs are more slowly translated. They also indicate that emergent polypeptides with as few as three basic residues within a ten-residue window tend to slow translation. With the improved mRNA measurements, the variation attributable to translational control in exponentially growing yeast was less than previously reported, and most of this variation could be predicted with a simple model that considered mRNA abundance, upstream open reading frames, cap-proximal structure and nucleotide composition, and lengths of the coding and 5' UTRs. Collectively, our results provide a framework for executing and interpreting ribosome-profiling studies and reveal key features of translational control in yeast.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: david.weinberg@ucsf.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Weinberg
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Premal
authors.initials: P
authors.lastname: Shah
authors.affiliation: Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Eichhorn
authors.affiliation: Institute for Computational Engineering and Sciences, University of Texas, Austin, TX 78712, USA; Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hussmann
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plotkin
authors.affiliation: Howard Hughes Medical Institute; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
mesh_terms: D020121:5' Untranslated Regions; D003062:Codon / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D015233:Models, Statistical; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D003062:Codon; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer