40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling.
40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling.
复制标题
40S 核糖体分析揭示了 Tma20/Tma22 (MCT-1/DENR) 和 Tma64 (eIF2D) 在 40S 亚基回收中的不同作用。
DOI：
10.1038/s41467-021-23223-8
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发表时间：
2021-05-20
影响因子：
16.6
通讯作者：
Guydosh NR
中科院分区：
文献类型：
--
作者：
Young DJ;Meydan S;Guydosh NR
核糖体在终止密码子处的再循环用于进一步的翻译循环对于有效的蛋白质合成是至关重要的。60 S亚基的去除由ATP酶Rli 1（ABCE 1）催化，而40 S的去除被认为需要Tma 64（eIF 2D）、Tma 20（MCT-1）和Tma 22（DENR）。然而，目前还不清楚这些Tma蛋白如何引起40 S去除和控制下游翻译的重新启动。在这里，我们使用40 S核糖体足迹策略来直接观察细胞中核糖体再循环的中间步骤。编码这些Tma蛋白的基因的缺失导致未回收的40 S亚基在终止密码子处的广泛积累，直接确立了它们在40 S回收中的作用。此外，Tma 20/Tma 22异源二聚体负责大部分40 S再循环事件，而Tma 64起次要作用。将自闭症相关突变引入TMA 22导致40 S再循环活性的丧失，将核糖体再循环和神经系统疾病联系起来。在终止密码子处翻译终止后，核糖体的真核60 S亚基被ATP酶ABCE 1去除。在这里，作者使用40 S核糖体足迹法直接证明了eIF 2D、MCT-1和DENR的酵母直向同源物回收40 S亚基。
The recycling of ribosomes at stop codons for use in further rounds of translation is critical for efficient protein synthesis. Removal of the 60S subunit is catalyzed by the ATPase Rli1 (ABCE1) while removal of the 40S is thought to require Tma64 (eIF2D), Tma20 (MCT-1), and Tma22 (DENR). However, it remains unclear how these Tma proteins cause 40S removal and control reinitiation of downstream translation. Here we used a 40S ribosome footprinting strategy to directly observe intermediate steps of ribosome recycling in cells. Deletion of the genes encoding these Tma proteins resulted in broad accumulation of unrecycled 40S subunits at stop codons, directly establishing their role in 40S recycling. Furthermore, the Tma20/Tma22 heterodimer was responsible for a majority of 40S recycling events while Tma64 played a minor role. Introduction of an autism-associated mutation into TMA22 resulted in a loss of 40S recycling activity, linking ribosome recycling and neurological disease. Following the termination of translation at stop codons, the eukaryotic 60S subunit of the ribosome is removed by the ATPase ABCE1. Here using 40S ribosome footprinting the authors provide a direct demonstration that the yeast orthologs of eIF2D, MCT-1, and DENR recycle the 40S subunits.
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