Phosphorylation of Pal2 by the protein kinases Kin1 and Kin2 modulates HAC1 mRNA splicing in the unfolded protein response in yeast.

Autor:	Ghosh C; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA., Uppala JK; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA., Sathe L; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA., Hammond CI; Department of Biological Sciences, Quinnipiac University, Hamden, CT 06518, USA., Anshu A; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA., Pokkuluri PR; Bioscience Division, Argonne National Laboratory, Lemont, IL 60439, USA., Turk BE; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA., Dey M; Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA. deym@uwm.edu.
Jazyk:	angličtina
Zdroj:	Science signaling [Sci Signal] 2021 May 25; Vol. 14 (684). Date of Electronic Publication: 2021 May 25.
DOI:	10.1126/scisignal.aaz4401
Abstrakt:	During cellular stress in the budding yeast Saccharomyces cerevisiae , an endoplasmic reticulum (ER)-resident dual kinase and RNase Ire1 splices an intron from HAC1 mRNA in the cytosol, thereby releasing its translational block. Hac1 protein then activates an adaptive cellular stress response called the unfolded protein response (UPR) that maintains ER homeostasis. The polarity-inducing protein kinases Kin1 and Kin2 contribute to HAC1 mRNA processing. Here, we showed that an RNA-protein complex that included the endocytic proteins Pal1 and Pal2 mediated HAC1 mRNA splicing downstream of Kin1 and Kin2. We found that Pal1 and Pal2 bound to the 3' untranslated region (3'UTR) of HAC1 mRNA, and a yeast strain lacking both Pal1 and Pal2 was deficient in HAC1 mRNA processing. We also showed that Kin1 and Kin2 directly phosphorylated Pal2, and that a nonphosphorylatable Pal2 mutant could not rescue the UPR defect in a pal1 Δ pal2 Δ strain. Thus, our work uncovers a Kin1/2-Pal2 signaling pathway that coordinates HAC1 mRNA processing and ER homeostasis. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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