Translational Regulation of Pmt1 and Pmt2 by Bfr1 Affects Unfolded Protein O-Mannosylation
by
Joan Castells-Ballester 1, Natalie Rinis 1
, Ilgin Kotan 2, Lihi Gal 3, Daniela Bausewein 1,4, Ilia Kats 2, Ewa Zatorska 1, Günter Kramer 2, Bernd Bukau 2, Maya Schuldiner 3 and Sabine Strahl 1,*
Joan Castells-Ballester 1, Natalie Rinis 1, Ilgin Kotan 2, Lihi Gal 3, Daniela Bausewein 1,4, Ilia Kats 2, Ewa Zatorska 1, Günter Kramer 2, Bernd Bukau 2, Maya Schuldiner 3 and Sabine Strahl 1,*
1
Centre for Organismal Studies (COS), Glycobiology, Heidelberg University, D-69120 Heidelberg, Germany
2
Center for Molecular Biology of Heidelberg University (ZMBH), German Cancer Research Center (DKFZ), ZMBH-DKFZ Alliance, D-69120 Heidelberg, Germany
3
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel
4
spm2—Safety Projects & More GmbH, D-69493 Hirschberg a. d. Bergstraße, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6220; https://doi.org/10.3390/ijms20246220
Received: 15 November 2019 / Revised: 5 December 2019 / Accepted: 6 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue Protein Glycosylation in the Secretory Pathway: Variation, Biosynthesis and Function)
O-mannosylation is implicated in protein quality control in Saccharomyces cerevisiae due to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile folding cycles and saves cellular resources is mainly mediated by protein O-mannosyltransferases Pmt1 and Pmt2. Here we describe a genetic screen for factors that influence O-mannosylation in yeast, using slow-folding green fluorescent protein (GFP) as a reporter. Our screening identifies the RNA binding protein brefeldin A resistance factor 1 (Bfr1) that has not been linked to O-mannosylation and ER protein quality control before. We find that Bfr1 affects O-mannosylation through changes in Pmt1 and Pmt2 protein abundance but has no effect on PMT1 and PMT2 transcript levels, mRNA localization to the ER membrane or protein stability. Ribosome profiling reveals that Bfr1 is a crucial factor for Pmt1 and Pmt2 translation thereby affecting unfolded protein O-mannosylation. Our results uncover a new level of regulation of protein quality control in the secretory pathway.
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Keywords:
Bfr1; endoplasmic reticulum; mannosyltransferase; RNA binding; O-mannosylation; Pmt; protein quality control; translation; UPOM
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MDPI and ACS Style
Castells-Ballester, J.; Rinis, N.; Kotan, I.; Gal, L.; Bausewein, D.; Kats, I.; Zatorska, E.; Kramer, G.; Bukau, B.; Schuldiner, M.; Strahl, S. Translational Regulation of Pmt1 and Pmt2 by Bfr1 Affects Unfolded Protein O-Mannosylation. Int. J. Mol. Sci. 2019, 20, 6220.
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