Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan.
Cell Rep. 2012 Sep 27;2(3):447-53. doi: 10.1016/j.celrep.2012.08.010. Epub 2012 Sep 13.
Because messenger RNAs without a stop codon (nonstop mRNAs) generate stalled ribosomes, cells have developed a mechanism allowing degradation of nonstop mRNAs and their translation products (nonstop proteins) in the cytosol. Here, we observe the fate of nonstop proteins destined for organelles such as the endoplasmic reticulum (ER) and mitochondria. Nonstop mRNAs for secretory-pathway proteins in yeast generate nonstop proteins that become stuck in the translocator, the Sec61 complex, in the ER membrane. These stuck nonstop secretory proteins avoid proteasomal degradation in the cytosol, but are instead released into the ER lumen through stalled ribosome and translocator channels by Dom34:Hbs1. We also found that nonstop mitochondrial proteins are cleared from the mitochondrial translocator, the TOM40 complex, by Dom34:Hbs1. Clearance of stuck nonstop proteins from organellar translocator channels is crucial for normal protein influx into organelles and for normal cell growth, especially when nonstop mRNA decay does not function efficiently.
由于没有终止密码子的信使 RNA（无终止 mRNA）会生成停滞的核糖体，因此细胞已经开发出一种机制，允许在细胞质中降解无终止 mRNA 和它们的翻译产物（无终止蛋白）。在这里，我们观察了注定要进入内质网（ER）和线粒体等细胞器的无终止蛋白的命运。酵母中分泌途径蛋白的无终止 mRNA 会产生无终止蛋白，这些蛋白会卡在 Sec61 复合物的易位器中，即内质网膜中的易位器。这些卡在易位器中的无终止分泌蛋白避免了在细胞质中的蛋白酶体降解，而是通过停滞的核糖体和易位器通道由 Dom34:Hbs1 释放到内质网腔中。我们还发现，无终止线粒体蛋白通过 Dom34:Hbs1 从线粒体易位器，即 TOM40 复合物中被清除。从细胞器易位器通道中清除卡住的无终止蛋白对于正常的蛋白流入细胞器和正常的细胞生长至关重要，特别是在无终止 mRNA 降解不能有效发挥作用时。
