Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p/Ern4p that activates the unfolded protein response
Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p/Ern4p that activates the unfolded protein response
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DOI：
10.1091/mbc.8.10.1845
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发表时间：
1997-10-01
影响因子：
3.3
通讯作者：
Mori, K
中科院分区：
文献类型：
--
作者：
Kawahara, T;Yanagi, H;Mori, K
从内质网（ER）到细胞核的细胞内信号传导，称为未折叠蛋白反应（UPR），当未折叠蛋白在各种应激条件下（“ER应激”）在ER中积累时被激活。我们和其他人最近确定了Hac 1 p/Em 4p作为一个转录因子负责的UPR在酿酒酵母。进一步报道，Hac 1 p（238 aa）仅在ER应激的细胞中检测到，并且其表达由Hac 1前体mRNA的非常规剪接介导。剪接取代了Hac 1 p的C-末端部分;有人提出前体mRNA也被翻译，但230 aa的推定产物被泛素-蛋白酶体途径迅速降解。我们已经鉴定和表征了相同的调节剪接，并确认了其基本特征。然而，与上述建议相反，我们发现成熟mRNA的238-aa产物和所测试的230-aa型蛋白质是高度不稳定的，在稳定性上几乎没有差异或没有差异。此外，我们证明，在非应激细胞中Hac 1 p的缺乏是由于缺乏前体mRNA的翻译。我们的结论是，Hac 1 p的合成作为ER应激诱导的mRNA剪接的结果，导致激活的UPR。
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/Em4p as a transcription factor responsible for the UPR in Saccharomyces cevevisiae. It was further reported that Hac1p (238 aa) is detected only in ER-stressed cells, and its expression is mediated by unconventional splicing of HAC1 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.