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Vms1p is a release factor for the Ribosome-associated Quality control Complex

Olga Zurita Rendón, Eric K. Fredrickson, Conor J. Howard, Jonathan Van Vranken, Sarah Fogarty, Neal D. Tolley, Raghav Kalia, Beatriz A. Osuna, Peter S. Shen, Christopher P. Hill, View ORCID ProfileAdam Frost, Jared Rutter
doi: https://doi.org/10.1101/301341
Olga Zurita Rendón
1Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Eric K. Fredrickson
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Conor J. Howard
3Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158 USA
6California Institute for Quantitative Biomedical Research, San Francisco, CA 94158 USA
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Jonathan Van Vranken
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Sarah Fogarty
1Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Neal D. Tolley
4Molecular Medicine Program, University of Utah, Salt Lake City, UT, 84112, USA
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Raghav Kalia
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
3Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158 USA
6California Institute for Quantitative Biomedical Research, San Francisco, CA 94158 USA
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Beatriz A. Osuna
3Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158 USA
5Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158 USA
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Peter S. Shen
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Christopher P. Hill
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Adam Frost
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
3Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158 USA
6California Institute for Quantitative Biomedical Research, San Francisco, CA 94158 USA
7Chan Zuckerberg Biohub, San Francisco, CA 94158 USA
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  • ORCID record for Adam Frost
Jared Rutter
1Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
2Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
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Abstract

Eukaryotic cells employ the Ribosome-associated Quality control Complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, and the novel proteins Rqc1p and Rqc2p1–3. Following recognition and subunit splitting of stalled ribosomes, the RQC detects and assembles on 60S subunits that hold incomplete polypeptides linked to a tRNA (60S:peptidyl–tRNA)4–8. Ltn1p cooperates with Rqc1p to facilitate ubiquitination of the incomplete nascent chain, marking it for degradation7,9,10. Rqc2p stabilizes Ltn1p on the 60S3–5,8 and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with Carboxy-terminal Alanine and Threonine extensions, or CAT tails, via a mechanism that is distinct from canonical translation4,10. CAT-tailing mobilizes and exposes lysine residues in the nascent chain, especially those stalled within the exit tunnel, thereby supporting efficient ubiquitination10,11. If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains aggregate in the cytosol or within organelles like the mitochondria12–14. Here we identify Vms1p as the tRNA hydrolase that releases nascent polypeptides for extraction and degradation in the RQC pathway.

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Posted April 14, 2018.
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Vms1p is a release factor for the Ribosome-associated Quality control Complex
Olga Zurita Rendón, Eric K. Fredrickson, Conor J. Howard, Jonathan Van Vranken, Sarah Fogarty, Neal D. Tolley, Raghav Kalia, Beatriz A. Osuna, Peter S. Shen, Christopher P. Hill, Adam Frost, Jared Rutter
bioRxiv 301341; doi: https://doi.org/10.1101/301341
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Vms1p is a release factor for the Ribosome-associated Quality control Complex
Olga Zurita Rendón, Eric K. Fredrickson, Conor J. Howard, Jonathan Van Vranken, Sarah Fogarty, Neal D. Tolley, Raghav Kalia, Beatriz A. Osuna, Peter S. Shen, Christopher P. Hill, Adam Frost, Jared Rutter
bioRxiv 301341; doi: https://doi.org/10.1101/301341

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