Local translation of yeast ERG4 mRNA at the endoplasmic reticulum requires the brefeldin A resistance protein Bfr1

Manchalu, Srinivas and Mittal, Nitish and Spang, Anne and Jansen, Ralf-Peter. (2019) Local translation of yeast ERG4 mRNA at the endoplasmic reticulum requires the brefeldin A resistance protein Bfr1. RNA, 25 (12). pp. 1661-1672.

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Brefeldin A resistance factor 1 (Bfr1p) is a non-essential RNA-binding protein and multi-copy suppressor of brefeldin A sensitivity in Saccharomyces cerevisiae. Deletion of BFR1 leads to multiple defects, including altered cell shape and size, change in ploidy, induction of P-bodies and chromosomal mis-segregation. Bfr1p has been shown to associate with polysomes, binds to several hundred mRNAs, and can target some of them to P-bodies. Although this implies a role of Bfr1p in translational control of mRNAs, its molecular function remains elusive. In the present study, we show that mutations in RNA-binding residues of Bfr1p impede its RNA-dependent co-localization with ER, yet do not mimic the known cellular defects seen upon BFR1 deletion. However, a Bfr1 RNA-binding mutant is impaired in binding to ERG4 mRNA which encodes an enzyme required for the final step of ergosterol biosynthesis. Consistently, bfr1∆ strains show a strong reduction in Erg4p protein levels, most likely due to degradation of misfolded Erg4p. Polysome profiling of bfr1∆ or bfr1 mutant strains reveals a strong shift of ERG4 mRNA to polysomes, consistent with a function of Bfr1p in elongation or increased ribosome loading. Collectively, our data reveal that Bfr1 has at least two separable functions: one in RNA-binding and co-translational protein translocation into the ER, and one in ploidy control or chromosome segregation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spang)
UniBasel Contributors:Spang, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:RNA Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2021 10:21
Deposited On:01 Feb 2021 10:21

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