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 pal1Δ pal2Δ strain. Thus, our work uncovers a Kin1/2-Pal2 signaling pathway that coordinates HAC1 mRNA processing and ER homeostasis.

在出芽酵母酿酒酵母的细胞应激过程中，内质网 (ER) 驻留的双重激酶和 RNase Ire1 从胞质溶胶中的 HAC1 mRNA 剪接一个内含子，从而释放其翻译块。Hac1 蛋白随后会激活一种称为未折叠蛋白反应 (UPR) 的适应性细胞应激反应，以维持 ER 稳态。极性诱导蛋白激酶 Kin1 和 Kin2 有助于HAC1 mRNA 加工。在这里，我们展示了一个包含内吞蛋白 Pal1 和 Pal2 的 RNA 蛋白复合物介导了Kin1和 Kin2 下游的 HAC1 mRNA 剪接。我们发现 Pal1 和 Pal2 与 HAC1 的 3' 非翻译区 (3'UTR)结合mRNA 和同时缺乏 Pal1 和 Pal2 的酵母菌株缺乏HAC1 mRNA 加工。我们还发现 Kin1 和 Kin2 直接磷酸化 Pal2，并且不可磷酸化的 Pal2 突变体无法挽救 pal1 Δ pal2 Δ 菌株中的 UPR 缺陷。因此，我们的工作揭示了协调HAC1 mRNA 加工和 ER 稳态的 Kin1/2-Pal2 信号通路。