Stress granules are dynamic assemblies of proteins and nontranslating RNAs that form when translation is inhibited in response to diverse stresses. Defects in ubiquitin–proteasome system factors including valosin-containing protein (VCP) and the proteasome impact the kinetics of stress granule induction and dissolution as well as being implicated in neuropathogenesis. However, the impacts of dysregulated proteostasis on mRNA regulation and stress granules are not well understood. Using single mRNA imaging, we discovered ribosomes stall on some mRNAs during arsenite stress, and the release of transcripts from stalled ribosomes for their partitioning into stress granules requires the activities of VCP, components of the ribosome-associated quality control (RQC) complex, and the proteasome. This is an unexpected contribution of the RQC system in releasing mRNAs from translation under stress, thus identifying a new type of stress-activated RQC (saRQC) distinct from canonical RQC pathways in mRNA substrates, cellular context, and mRNA fate.

中文翻译：

---

翻译质量控制和针对应激颗粒的 mRNA 的耦合

应激颗粒是蛋白质和非翻译 RNA 的动态组装体，当翻译因各种应激而受到抑制时形成。泛素-蛋白酶体系统因子（包括含缬洛辛蛋白（VCP）和蛋白酶体）的缺陷会影响应激颗粒诱导和溶解的动力学，并与神经发病机制有关。然而，蛋白质稳态失调对 mRNA 调节和应激颗粒的影响尚不清楚。使用单 mRNA 成像，我们发现在亚砷酸盐胁迫期间，核糖体在某些 mRNA 上停滞，并且从停滞的核糖体释放转录本以分配到应激颗粒中需要 VCP 的活性，VCP 是核糖体相关质量控制 (RQC) 复合物的组成部分，并且蛋白酶体。这是 RQC 系统在压力下从翻译中释放 mRNA 方面的意外贡献，从而识别出一种新型压力激活 RQC (saRQC)，其与 mRNA 底物、细胞背景和 mRNA 命运中的典型 RQC 途径不同。