ZMBH, University of Heidelberg, 69120 Heidelberg, Germany; email:
The Scripps Research Institute, La Jolla, California 92037.
Annu Rev Cell Dev Biol. 2017 Oct 6;33:343-368. doi: 10.1146/annurev-cellbio-111315-125249. Epub 2017 Jul 17.
Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits. As a final critical step in this pathway, the Ltn1/Listerin E3 ligase subunit of the RQC complex (RQCc) ubiquitylates the nascent chain, which promotes clearance of the 60S subunit while simultaneously marking the nascent chain for elimination. Here we review the ribosomal stalling and rescue steps upstream of the RQCc, where one witnesses intersection with cellular machineries implicated in translation elongation, translation termination, ribosomal subunit recycling, and mRNA quality control. We emphasize both recent progress and future directions in this area, as well as examples linking ribosomal rescue with the production of Ltn1-RQCc substrates.
所有生物体的细胞都在翻译延伸过程中检测问题，这些问题可能是由于 mRNA 异常、解码效率低下或其他原因引起的。在真核生物中，核糖体相关的质量控制 (RQC) 可以感应延伸停滞的核糖体，并促进核糖体亚基的解离。这种所谓的核糖体拯救释放出 mRNA 进行降解，并允许 40S 亚基循环用于新的翻译回合。然而，新生多肽链仍然与 tRNA 相连，并与被拯救的 60S 亚基相关联。作为该途径的最后一个关键步骤，RQC 复合物 (RQCc) 的 Ltn1/Listerin E3 连接酶亚基将新生链泛素化，这促进了 60S 亚基的清除，同时标记新生链进行消除。在这里，我们回顾了 RQCc 上游的核糖体停滞和拯救步骤，在这些步骤中，人们可以看到与翻译延伸、翻译终止、核糖体亚基回收和 mRNA 质量控制相关的细胞机制的交叉。我们强调了该领域的最新进展和未来方向，以及将核糖体拯救与 Ltn1-RQCc 底物的产生联系起来的例子。
