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Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation

David E. Weinberg, Premal Shah, Stephen W. Eichhorn, Jeffrey A. Hussmann, Joshua B. Plotkin, David P. Bartel
doi: https://doi.org/10.1101/021501
David E. Weinberg
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
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  • For correspondence: david.weinberg@ucsf.edu
Premal Shah
2Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 USA
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Stephen W. Eichhorn
3Howard Hughes Medical Institute
4Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
5Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Jeffrey A. Hussmann
6Institute for Computational Engineering and Sciences, University of Texas, Austin, TX 78712, USA
7Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA
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Joshua B. Plotkin
2Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 USA
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David P. Bartel
3Howard Hughes Medical Institute
4Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
5Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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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 10-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’-untranslated regions. Collectively, our results reveal key features of translational control in yeast and provide a framework for executing and interpreting ribosome-profiling studies.

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  • ↵* Co-first authors

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Posted July 06, 2015.
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Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation
David E. Weinberg, Premal Shah, Stephen W. Eichhorn, Jeffrey A. Hussmann, Joshua B. Plotkin, David P. Bartel
bioRxiv 021501; doi: https://doi.org/10.1101/021501
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Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation
David E. Weinberg, Premal Shah, Stephen W. Eichhorn, Jeffrey A. Hussmann, Joshua B. Plotkin, David P. Bartel
bioRxiv 021501; doi: https://doi.org/10.1101/021501

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