Protein quality control systems associated with no-go and nonstop mRNA surveillance in yeast
Protein quality control systems associated with no-go and nonstop mRNA surveillance in yeast
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DOI：
10.1111/gtc.12106
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发表时间：
2014-01-01
期刊：
影响因子：
2.1
通讯作者：
Inada, Toshifumi
中科院分区：
文献类型：
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作者：
Matsuda, Ryo;Ikeuchi, Ken;Inada, Toshifumi
质量控制系统消除源自异常mRNA的异常蛋白质。两个E3泛素连接酶，Ltn1和Not4，参与蛋白酶体蛋白降解耦合翻译停滞。在这里，我们评估了不停止和翻译停滞产品降解聚（A）尾独立的方式。Ltn1被发现降解来自不停止mRNA的异常不停止多肽缺乏终止密码子，但不是肽基-tRNA，即使在没有核糖体解离复合物Dom34：Hbs1。活化C激酶受体（RACK1/ASC1）被鉴定为新生肽依赖性翻译停滞以及Ltn1依赖性蛋白质降解所需的因子。Not4和Ltn1均以不依赖于poly（A）尾的方式参与各种阻滞产物的降解。此外，羧基末端截短的降解中间产物的逮捕稳定在cdc48 - 3突变体的展开或拆卸相关的蛋白酶体降解缺陷。因此，我们建议，停滞的核糖体可能被解离成亚基和60 S亚基上的肽基-tRNA是泛素化的Ltn1和Cdc48是必需的降解后释放的tRNA。
Quality control systems eliminate aberrant proteins derived from aberrant mRNAs. Two E3 ubiquitin ligases, Ltn1 and Not4, are involved in proteasomal protein degradation coupled to translation arrest. Here, we evaluated nonstop and translation arrest products degraded in a poly(A) tail-independent manner. Ltn1 was found to degrade aberrant nonstop polypeptides derived from nonstop mRNA lacking a termination codon, but not peptidyl-tRNA, even in the absence of the ribosome dissociation complex Dom34:Hbs1. The receptor for activated C kinase (RACK1/ASC1) was identified as a factor required for nascent peptide-dependent translation arrest as well as Ltn1-dependent protein degradation. Both Not4 and Ltn1 were involved in the degradation of various arrest products in a poly(A) tail-independent manner. Furthermore, carboxyl terminus-truncated degradation intermediates of arrest products were stabilized in a cdc48-3 mutant defective in unfolding or the disassembly related to proteasomal degradation. Thus, we propose that stalled ribosomes may be dissociated into subunits and that peptidyl-tRNA on the 60S subunit is ubiquitinated by Ltn1 and Cdc48 is required for the degradation following release from tRNA.