Coupled protein quality control during nonsense-mediated mRNA decay.
Coupled protein quality control during nonsense-mediated mRNA decay.
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DOI：
10.1242/jcs.261216
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发表时间：
2023-05-15
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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含有提前终止密码子（PTC）的mRNA的翻译导致具有有害作用的截短的蛋白质产物。无义介导的衰变（NMD）是负责检测含有转录本的PTC的监视途径。虽然mRNA降解的分子机制已被广泛研究，但新生蛋白质产物的命运在很大程度上仍不确定。在这里，我们在哺乳动物细胞中使用荧光报告系统，以揭示一个选择性的降解途径，专门针对NMD mRNA的蛋白质产物。我们发现，这一过程是翻译后和依赖于泛素蛋白酶体系统。为了系统地揭示参与NMD连锁蛋白质质量控制的因素，我们进行了全基因组流式细胞术为基础的屏幕。我们的筛选恢复了已知的NMD因子，但表明蛋白质降解不依赖于经典的核糖体质量控制（RQC）途径。随后的阵列筛选表明，NMD的蛋白质和mRNA分支依赖于共享的识别事件。我们的研究结果建立了一个有针对性的途径，新生蛋白质降解含PTC的mRNA，并提供了一个参考领域，以确定和表征所需的因素。总结：无义介导的mRNA衰变利用偶联的蛋白质质量控制途径来协调异常mRNA及其相关新生多肽链的降解。
Translation of mRNAs containing premature termination codons (PTCs) results in truncated protein products with deleterious effects. Nonsense-mediated decay (NMD) is a surveillance pathway responsible for detecting PTC containing transcripts. Although the molecular mechanisms governing mRNA degradation have been extensively studied, the fate of the nascent protein product remains largely uncharacterized. Here, we use a fluorescent reporter system in mammalian cells to reveal a selective degradation pathway specifically targeting the protein product of an NMD mRNA. We show that this process is post-translational and dependent on the ubiquitin proteasome system. To systematically uncover factors involved in NMD-linked protein quality control, we conducted genome-wide flow cytometry-based screens. Our screens recovered known NMD factors but suggested that protein degradation did not depend on the canonical ribosome-quality control (RQC) pathway. A subsequent arrayed screen demonstrated that protein and mRNA branches of NMD rely on a shared recognition event. Our results establish the existence of a targeted pathway for nascent protein degradation from PTC containing mRNAs, and provide a reference for the field to identify and characterize required factors. Summary: Nonsense-mediated mRNA decay utilizes a coupled protein quality control pathway to coordinate degradation of both the aberrant mRNA and its associated nascent polypeptide chain.
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影响因子：
16
作者：
Feng Q;Jagannathan S;Bradley RK
通讯作者：
Bradley RK
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：
16.8
作者：
Ballut, L;Marchadier, B;Le Hir, H
通讯作者：
Le Hir, H
影响因子：
10.5
作者：
Czaplinski, K;Ruiz-Echevarria, MJ;Peltz, SW
通讯作者：
Peltz, SW
影响因子：
64.8
作者：
Amrani, N;Ganesan, R;Jacobson, A
通讯作者：
Jacobson, A