scholarly journals RTCB-1 Mediates Neuroprotection via XBP-1 mRNA Splicing in the Unfolded Protein Response Pathway

2014 ◽  
Vol 34 (48) ◽  
pp. 16076-16085 ◽  
Author(s):  
A. Ray ◽  
S. Zhang ◽  
C. Rentas ◽  
K. A. Caldwell ◽  
G. A. Caldwell
Keyword(s):  
Unfolded Protein Response ◽  
Mrna Splicing ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

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

2021 ◽  
Vol 14 (684) ◽  
pp. eaaz4401
Author(s):  
Chandrima Ghosh ◽  
Jagadeesh Kumar Uppala ◽  
Leena Sathe ◽  
Charlotte I. Hammond ◽  
Ashish Anshu ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Protein Kinases ◽  
Cellular Stress ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Cellular Stress Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis

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.

scholarly journals Endoplasmic Reticulum Stress-induced mRNA Splicing Permits Synthesis of Transcription Factor Hac1p/Ern4p That Activates the Unfolded Protein Response

1997 ◽  
Vol 8 (10) ◽  
pp. 1845-1862 ◽  
Author(s):  
Tetsushi Kawahara ◽  
Hideki Yanagi ◽  
Takashi Yura ◽  
Kazutoshi Mori
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Intracellular Signaling ◽  
Mrna Splicing ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Precursor Mrna

An intracellular signaling from the endoplasmic reticulum (ER) to the nucleus, called the unfolded protein response (UPR), is activated when unfolded proteins are accumulated in the ER under a variety of stress conditions (“ER stress”). We and others recently identified Hac1p/Ern4p as a transcription factor responsible for the UPR inSaccharomyces cerevisiae. It was further reported that Hac1p (238 aa) is detected only in ER-stressed cells, and its expression is mediated by unconventional splicing ofHAC1 precursor mRNA. The splicing replaces the C-terminal portion of Hac1p; it was proposed that precursor mRNA is also translated but the putative product of 230 aa is rapidly degraded by the ubiquitin–proteasome pathway. We have identified and characterized the same regulated splicing and confirmed its essential features. Contrary to the above proposal, however, we find that the 238-aa product of mature mRNA and the 230-aa-type protein tested are highly unstable with little or no difference in stability. Furthermore, we demonstrate that the absence of Hac1p in unstressed cells is due to the lack of translation of precursor mRNA. We conclude that Hac1p is synthesized as the result of ER stress-induced mRNA splicing, leading to activation of the UPR.

scholarly journals Splicing HAC1/XBP1 mRNAs in Cytoplasm: The Non-Conventional mRNA Splicing Reaction in the Unfolded Protein Response

2020 ◽  
Vol 4 (2) ◽  
pp. 1-11
Author(s):  
Yi Song ◽  
◽  
Carlos Rivera ◽  
Jiayu Mai ◽  
Annie Sun ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Mrna Splicing ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals tRNA Ligase Is Required for Regulated mRNA Splicing in the Unfolded Protein Response

Cell ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 405-413 ◽  
Author(s):  
Carmela Sidrauski ◽  
Jeffery S Cox ◽  
Peter Walter
Keyword(s):  
Unfolded Protein Response ◽  
Mrna Splicing ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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