Unfolded Protein Response Suppression in Yeast by Loss of tRNA Modifications.
Unfolded Protein Response Suppression in Yeast by Loss of tRNA Modifications.
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DOI：
10.3390/genes9110516
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发表时间：
2018-10-23
期刊：
影响因子：
3.5
通讯作者：
Schaffrath R
中科院分区：
文献类型：
--
作者：
Bruch A;Klassen R;Schaffrath R
转移RNA（tRNA）的反密码子环的修饰已被证明可以确保最佳的密码子翻译速率，并防止因翻译暂停而出现的蛋白质稳态缺陷。因此，几个缺乏重要的反密码子环修饰的酵母突变体显示积累蛋白质聚集体。在这里，我们分析这是否包括未折叠蛋白反应（UPR）的激活，这通常是由内质网（ER）内的蛋白质聚集引发的。我们证明，两种不同的聚集倾向tRNA修饰突变体（elp 6 ncs 2; elp 3 deg 1）缺乏5-甲氧羰基甲基-2-硫尿苷（mcm 5s 2U：elp 3; elp 6; ncs 2）和假尿苷（pseudoduridine：deg 1）的组合减少，而不是增加，剪接的HAC 1 mRNA，一个事件通常发生的UPR诱导的先决条件。此外，衣霉素（TM）诱导的HAC 1剪接在elp 3 deg 1突变体中强烈受损。引人注目的是，该突变体显示出对TM的UPR非依赖性抗性，我们发现这种表型通过tRNAGln（UUG）的过表达而被拯救，tRNAGln（UUG）是通常携带mcm 5s 2U 34和mcm 5s 38修饰的tRNA种类。我们的数据表明，适当的tRNA反密码子环修饰促进而不是损害UPR激活，并揭示蛋白质合成和稳态缺陷，在他们的情况下，通常不会导致UPR诱导，但可能会减轻内源性ER应激。
Modifications in the anticodon loop of transfer RNAs (tRNAs) have been shown to ensure optimal codon translation rates and prevent protein homeostasis defects that arise in response to translational pausing. Consequently, several yeast mutants lacking important anticodon loop modifications were shown to accumulate protein aggregates. Here we analyze whether this includes the activation of the unfolded protein response (UPR), which is commonly triggered by protein aggregation within the endoplasmic reticulum (ER). We demonstrate that two different aggregation prone tRNA modification mutants (elp6 ncs2; elp3 deg1) lacking combinations of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U: elp3; elp6; ncs2) and pseudouridine (Ψ: deg1) reduce, rather than increase, splicing of HAC1 mRNA, an event normally occurring as a precondition of UPR induction. In addition, tunicamycin (TM) induced HAC1 splicing is strongly impaired in the elp3 deg1 mutant. Strikingly, this mutant displays UPR independent resistance against TM, a phenotype we found to be rescued by overexpression of tRNAGln(UUG), the tRNA species usually carrying the mcm5s2U34 and Ψ38 modifications. Our data indicate that proper tRNA anticodon loop modifications promote rather than impair UPR activation and reveal that protein synthesis and homeostasis defects in their absence do not routinely result in UPR induction but may relieve endogenous ER stress.
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影响因子：
3.3
作者：
Damon JR;Pincus D;Ploegh HL
通讯作者：
Ploegh HL
DOI：
10.1261/rna.048173.114
发表时间：
2015-02
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Han L;Kon Y;Phizicky EM
通讯作者：
Phizicky EM
影响因子：
11.8
作者：
Laguesse, Sophie;Creppe, Catherine;Nguyen, Laurent
通讯作者：
Nguyen, Laurent
影响因子：
4.8
作者：
Kojic M;Wainwright B
通讯作者：
Wainwright B
影响因子：
2.1
作者：
Mori, K;Kawahara, T;Yura, T
通讯作者：
Yura, T