Is there a localized role for translational quality control?

Is there a localized role for translational quality control?
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翻译质量控制是否有本地化的角色?

DOI:
10.1261/rna.079683.123
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发表时间:
2023-11
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
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中科院分区:
其他
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已知mRNA和翻译它们的机制在整个细胞质中不是均匀分布的。因此,一些基因的表达定位于细胞的特定部分,这使得在三维空间中进行重要活动,如生长和信号传导成为可能。然而,局部基因表达的功能尚未完全理解,并且在许多情况下,使局部表达成为可能的潜在机制尚未确定。有助于解决这些挑战的一个考虑因素是监测翻译核糖体的质量控制(QC)机制的作用。在全球范围内,QC途径对于检测异常翻译事件(例如在翻译时停滞的核糖体)以及通过激活应激途径和在分子水平上解决有问题的核糖体和mRNA来响应至关重要。然而,目前还不清楚这些途径,即使在整个细胞中均匀活跃,如何影响局部翻译。重要的是,据报道,一些QC途径本身在特定细胞器附近富集,但这种局部活性的程度在很大程度上仍然未知。在这里,我们描述了主要的质量控制途径,并回顾了已经开始探索其在本地化翻译中的作用的研究。鉴于这一领域的数据有限,我们还提出了关于QC途径如何促进细胞中局部基因表达的可能性和局限性的广泛问题,目的是为未来的实验提供思路。
It is known that mRNAs and the machinery that translates them are not uniformly distributed throughout the cytoplasm. As a result, the expression of some genes is localized to particular parts of the cell and this makes it possible to carry out important activities, such as growth and signaling, in three-dimensional space. However, the functions of localized gene expression are not fully understood, and the underlying mechanisms that enable localized expression have not been determined in many cases. One consideration that could help in addressing these challenges is the role of quality control (QC) mechanisms that monitor translating ribosomes. On a global level, QC pathways are critical for detecting aberrant translation events, such as a ribosome that stalls while translating, and responding by activating stress pathways and resolving problematic ribosomes and mRNAs at the molecular level. However, it is unclear how these pathways, even when uniformly active throughout the cell, affect local translation. Importantly, some QC pathways have themselves been reported to be enriched in the proximity of particular organelles, but the extent of such localized activity remains largely unknown. Here, we describe the major QC pathways and review studies that have begun to explore their roles in localized translation. Given the limited data in this area, we also pose broad questions about the possibilities and limitations for how QC pathways could facilitate localized gene expression in the cell with the goal of offering ideas for future experimentation.
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