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Identification of a localized nonsense-mediated decay pathway at the endoplasmic reticulum.
Genes & Development ( IF 7.5 ) Pub Date : 2020-08-01 , DOI: 10.1101/gad.338061.120
Dasa Longman 1 , Kathryn A Jackson-Jones 1 , Magdalena M Maslon 1 , Laura C Murphy 1 , Robert S Young 1 , Jack J Stoddart 1 , Nele Hug 1 , Martin S Taylor 1 , Dimitrios K Papadopoulos 1 , Javier F Cáceres 1
Affiliation  

Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously identified NBAS, a component of the Syntaxin 18 complex involved in Golgi-to-ER trafficking, as a novel NMD factor. Furthermore, we show that NBAS fulfills an independent function in NMD. This ER–NMD pathway requires the interaction of NBAS with the core NMD factor UPF1, which is partially localized at the ER in the proximity of the translocon. NBAS and UPF1 coregulate the stability of ER-associated transcripts, in particular those associated with the cellular stress response. We propose a model where NBAS recruits UPF1 to the membrane of the ER and activates an ER-dedicated NMD pathway, thus providing an ER-protective function by ensuring quality control of ER-translated mRNAs.

中文翻译:

内质网局部无义介导的衰变途径的鉴定。

无义介导的衰变 (NMD) 是一种发生在细胞质中的翻译依赖性 RNA 质量控制机制。然而,NMD 如何调节内质网 (ER) 翻译的 RNA 的稳定性尚不清楚。在这里,我们确定了一条专用于 ER 翻译 mRNA 的局部 NMD 通路。我们之前将 NBAS(参与高尔基体到 ER 运输的 Syntaxin 18 复合物的一个组成部分)确定为一种新型 NMD 因子。此外,我们还表明 NBAS 在 NMD 中发挥着独立的作用。该 ER-NMD 途径需要 NBAS 与核心 NMD 因子 UPF1 相互作用,该因子部分位于易位子附近的 ER 上。NBAS 和 UPF1 共同调节 ER 相关转录本的稳定性,特别是那些与细胞应激反应相关的转录本。我们提出了一个模型,其中 NBAS 将 UPF1 招募到 ER 膜上并激活 ER 专用的 NMD 途径,从而通过确保 ER 翻译的 mRNA 的质量控制来提供 ER 保护功能。
更新日期:2020-08-03
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