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Protein products of nonstop mRNA disrupt nucleolar homeostasis
Cell Stress and Chaperones ( IF 3.8 ) Pub Date : 2021-02-22 , DOI: 10.1007/s12192-021-01200-w
Zoe H Davis 1 , Laura Mediani 2 , Francesco Antoniani 2 , Jonathan Vinet 2 , Shuangxi Li 3 , Simon Alberti 4 , Bingwei Lu 3 , Alex S Holehouse 5, 6 , Serena Carra 2 , Onn Brandman 1
Affiliation  

Stalled mRNA translation results in the production of incompletely synthesized proteins that are targeted for degradation by ribosome-associated quality control (RQC). Here we investigated the fate of defective proteins translated from stall-inducing, nonstop mRNA that escape ubiquitylation by the RQC protein LTN1. We found that nonstop protein products accumulated in nucleoli and this localization was driven by polylysine tracts produced by translation of the poly(A) tails of nonstop mRNA. Nucleolar sequestration increased the solubility of invading proteins but disrupted nucleoli, altering their dynamics, morphology, and resistance to stress in cell culture and intact flies. Our work elucidates how stalled translation may affect distal cellular processes and may inform studies on the pathology of diseases caused by failures in RQC and characterized by nucleolar stress.



中文翻译:

不间断 mRNA 的蛋白质产物破坏核仁稳态

停滞的 mRNA 翻译导致产生不完全合成的蛋白质,这些蛋白质通过核糖体相关质量控制 (RQC) 进行降解。在这里,我们研究了从失速诱导、不间断 mRNA 翻译的缺陷蛋白的命运,这些 mRNA 逃脱了 RQC 蛋白 LTN1 的泛素化。我们发现在核仁中积累了不间断的蛋白质产物,并且这种本地化是由不间断 mRNA 的 poly(A) 尾部翻译产生的多聚赖氨酸大片驱动的。核仁隔离增加了入侵蛋白质的溶解度,但破坏了核仁,改变了它们在细胞培养和完整果蝇中的动力学、形态和对压力的抵抗力。

更新日期:2021-02-23
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