Loss of mRNA surveillance pathways results in widespread protein aggregation.
Loss of mRNA surveillance pathways results in widespread protein aggregation.
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DOI：
10.1038/s41598-018-22183-2
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发表时间：
2018-03-01
影响因子：
4.6
通讯作者：
Grant CM
中科院分区：
文献类型：
--
作者：
Jamar NH;Kritsiligkou P;Grant CM
真核细胞包含翻译相关的信使核糖核酸监视通路，可防止异常信使核糖核酸翻译事件产生潜在的毒性蛋白。我们发现，在缺乏无意义介导的衰变(NMD)、无意义衰变(NGD)和不停止衰变(NSD)的突变体中，mRNA监控通路的丢失会导致蛋白质聚集增加。我们已经分离和鉴定了聚集的蛋白质，我们的生物信息学分析表明，聚集倾向于蛋白质的聚集增加是mRNA监测突变体中的普遍现象，而不是归因于特定的途径。与更广泛的蛋白质组相比，聚集在mRNA监控突变体中的蛋白质往往更高表达、更丰富和更稳定。与新生蛋白质错误折叠反应中聚集的蛋白质也有很强的相关性，以及作为核糖体相关Hsp70伴侣蛋白底物的蛋白质的富集性，这与主要发生在翻译/折叠过程中的聚集易感性一致。我们还发现，在mRNA监控突变体和老化酵母细胞中聚集的蛋白质之间存在显着重叠，这表明翻译依赖的蛋白质聚集可能是衰老细胞群体中发生的蛋白稳定性丧失的一个特征。
Eukaryotic cells contain translation-associated mRNA surveillance pathways which prevent the production of potentially toxic proteins from aberrant mRNA translation events. We found that loss of mRNA surveillance pathways in mutants deficient in nonsense-mediated decay (NMD), no-go decay (NGD) and nonstop decay (NSD) results in increased protein aggregation. We have isolated and identified the proteins that aggregate and our bioinformatic analyses indicates that increased aggregation of aggregation-prone proteins is a general occurrence in mRNA surveillance mutants, rather than being attributable to specific pathways. The proteins that aggregate in mRNA surveillance mutants tend to be more highly expressed, more abundant and more stable proteins compared with the wider proteome. There is also a strong correlation with the proteins that aggregate in response to nascent protein misfolding and an enrichment for proteins that are substrates of ribosome-associated Hsp70 chaperones, consistent with susceptibility for aggregation primarily occurring during translation/folding. We also identified a significant overlap between the aggregated proteins in mRNA surveillance mutants and ageing yeast cells suggesting that translation-dependent protein aggregation may be a feature of the loss of proteostasis that occurs in aged cell populations.
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DOI：
10.1261/rna.060541.116
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Celik A;Baker R;He F;Jacobson A
通讯作者：
Jacobson A
影响因子：
8.8
作者：
Christiano R;Nagaraj N;Fröhlich F;Walther TC
通讯作者：
Walther TC
影响因子：
3.3
作者：
Peters TW;Rardin MJ;Czerwieniec G;Evani US;Reis-Rodrigues P;Lithgow GJ;Mooney SD;Gibson BW;Hughes RE
通讯作者：
Hughes RE
DOI：
10.1083/jcb.201612165
发表时间：
2017-08-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hamdan N;Kritsiligkou P;Grant CM
通讯作者：
Grant CM
影响因子：
4.8
作者：
Lum, R;Tkach, JM;Glover, JR
通讯作者：
Glover, JR