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Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable

36 Pages Posted: 5 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Keira Wiechecki

Keira Wiechecki

New York University (NYU) - Center for Genomics and Systems Biology

Sandhya Manohar

New York University (NYU) - Center for Genomics and Systems Biology

Gustavo Silva

New York University (NYU) - Center for Genomics and Systems Biology

Konstantine Tchourine

New York University (NYU) - Center for Genomics and Systems Biology

Samson Jacob

New York University (NYU) - School of Medicine

Angelo Valleriani

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Colloids and Interfaces

Christine Vogel

New York University (NYU) - Center for Genomics and Systems Biology

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Abstract

Measurements for protein half-lives in yeast Saccharomyces cerevisiae reported large discrepancies, with median values between minutes to several hours. We present a unifying analysis that provides a consistent half-life estimate, based on our re-analysis of three published and one new dataset of cells grown under similar conditions. We found that degradation of many proteins can be approximated by exponential decay. Protein disappearance was primarily driven by dilution due to cell division, with cell doubling times ranging from ~2 to 3.5 hours across the four experiments. After adjusting for doubling time, protein half-lives increased to median values between ~7.5 to ~40 hours. Half-lives correlated with cell doubling time even after adjustment, implying that slow growth also slows protein degradation. All estimates were validated by multiple means and were robust to different analysis methods. Overall, protein stability correlated with abundance and showed weak enrichment for degradation signals such as degrons and disordered regions. Long-lived proteins often functioned in oxidation-reduction and amino acid synthesis. Short-lived proteins often functioned in ribosome biogenesis. Despite some overall differences in behavior, all methods were able to resolve subtle difference in half-lives of ribosomal proteins, e.g. the short lifespan of RPL10. Finally, our results help the design of future experiments: time series measurements need to cover at least two to three cell doubling times for accurate estimates, exponential decay provides a reasonable proxy for protein stability, and it can be sufficiently estimated with four measurement points.

Suggested Citation

Wiechecki, Keira and Manohar, Sandhya and Silva, Gustavo and Tchourine, Konstantine and Jacob, Samson and Valleriani, Angelo and Vogel, Christine, Integrative Meta-Analysis Reveals That Most Yeast Proteins Are Very Stable (2018). Available at SSRN: https://ssrn.com/abstract=3155916 or http://dx.doi.org/10.2139/ssrn.3155916
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Keira Wiechecki

New York University (NYU) - Center for Genomics and Systems Biology

New York, NY
United States

Sandhya Manohar

New York University (NYU) - Center for Genomics and Systems Biology

New York, NY
United States

Gustavo Silva

New York University (NYU) - Center for Genomics and Systems Biology

New York, NY
United States

Konstantine Tchourine

New York University (NYU) - Center for Genomics and Systems Biology ( email )

New York, NY
United States

Samson Jacob

New York University (NYU) - School of Medicine

550 First Ave.
VZ30, Office 626
New York, NY 10016
United States

Angelo Valleriani

Max Planck Society for the Advancement of the Sciences - Max Planck Institute for Colloids and Interfaces

Potsdam-Golm Science Park
Am M├╝hlenberg 1 OT Golm
Potsdam, 14476
United States

Christine Vogel (Contact Author)

New York University (NYU) - Center for Genomics and Systems Biology ( email )

New York, NY
United States

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