C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly positive charge, PL stalls in the electrostatically negative ribosomal exit channel. The stalled polypeptide recruits the Ribosome-associated quality control (RQC) complex which processes and extracts the nascent chain. Dysfunction of the RQC leads to the accumulation of PL-tagged proteins, induction of a stress response, and cellular toxicity. Not much is known about the PL-specific aspect of protein quality control. Using quantitative mass spectrometry, we uncovered the post-ribosomal PL-processing machinery in human cytosol. It encompasses key cytosolic complexes of the proteostasis network, such as chaperonin TCP-1 ring complexes (TRiC) and half-capped 19S-20S proteasomes. Furthermore, we found that the nuclear transport machinery associates with PL, which suggests a novel mechanism by which faulty proteins can be compartmentalized in the cell. The enhanced nuclear import of a PL-tagged polypeptide confirmed this implication, which leads to questions regarding the biological rationale behind it.

中文翻译：

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聚赖氨酸是一种蛋白质稳态网络参与结构决定因素。

C-末端多聚赖氨酸 (PL) 可以从过早切割的 mRNA 的多聚腺嘌呤尾部合成，或者在发生终止密码子的通读时合成。由于高正电荷，PL 停滞在静电负核糖体出口通道中。停滞的多肽招募核糖体相关质量控制 (RQC) 复合物，该复合物处理和提取新生链。RQC 的功能障碍导致 PL 标记蛋白的积累、应激反应的诱导和细胞毒性。关于蛋白质质量控​​制的 PL 特定方面知之甚少。使用定量质谱，我们发现了人类细胞质中的核糖体后 PL 加工机制。它包含蛋白质稳态网络的关键胞质复合物，例如伴侣蛋白 TCP-1 环复合物 (TRiC) 和半封端 19S-20S 蛋白酶体。此外，我们发现核转运机制与 PL 相关，这表明了一种新的机制，通过该机制可以在细胞中划分有缺陷的蛋白质。增强的 PL 标记多肽的核输入证实了这一含义，这导致了对其背后的生物学原理的质疑。