Ribosome biogenesis factor Ltv1 chaperones the assembly of the small subunit head.
Ribosome biogenesis factor Ltv1 chaperones the assembly of the small subunit head.
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DOI：
10.1083/jcb.201804163
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发表时间：
2018-12-03
期刊：
影响因子：
--
通讯作者：
Karbstein K
中科院分区：
文献类型：
--
作者：
Collins JC;Ghalei H;Doherty JR;Huang H;Culver RN;Karbstein K
Collins等人利用酵母遗传学、生物化学和结构探针分析了组装因子Ltv1在40S核糖体成熟中的作用。来自Ltv1缺陷细胞的核糖体具有亚化学计量量的Rps10和Asc1以及错误折叠的头rRNA，导致翻译保真度和核糖体介导的RNA质量控制缺陷，表明Ltv1在陪伴亚基头组装中起作用。核糖体rna （RNAs）和核糖体蛋白（RPs）正确组装核糖体是至关重要的，正如癌细胞中RP单倍性不足和RP化学计量丧失引起的疾病所表明的那样。然而，如何确保每个RP的组装仍然知之甚少。我们利用酵母遗传学、生物化学和结构探测表明，组装因子Ltv1促进Rps3、Rps10和Asc1/RACK1进入小核糖体亚基头。来自ltv1缺陷酵母的核糖体具有亚化学计量量的Rps10和Asc1，并且在翻译保真度和核糖体介导的RNA质量控制方面存在缺陷。这些缺陷在某些条件下提供了生长优势，但使细胞对氧化应激敏感。有趣的是，与胶质瘤细胞系相比，乳腺癌细胞的LTV1水平降低，并产生缺乏RPS3、RPS10和RACK1的核糖体。这些数据描述了一种确保RP组装的机制，并展示了癌细胞如何绕过这一机制来产生不同的核糖体种群，从而促进应激下的生存。
Collins et al. use yeast genetics, biochemistry, and structure probing to dissect the role of the assembly factor Ltv1 in 40S ribosome maturation. Ribosomes from Ltv1-deficient cells have substoichiometric amounts of Rps10 and Asc1 and misfolded head rRNA, leading to defects in translational fidelity and ribosome-mediated RNA quality control, demonstrating a role for Ltv1 in chaperoning the assembly of the subunit head. The correct assembly of ribosomes from ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) is critical, as indicated by the diseases caused by RP haploinsufficiency and loss of RP stoichiometry in cancer cells. Nevertheless, how assembly of each RP is ensured remains poorly understood. We use yeast genetics, biochemistry, and structure probing to show that the assembly factor Ltv1 facilitates the incorporation of Rps3, Rps10, and Asc1/RACK1 into the small ribosomal subunit head. Ribosomes from Ltv1-deficient yeast have substoichiometric amounts of Rps10 and Asc1 and show defects in translational fidelity and ribosome-mediated RNA quality control. These defects provide a growth advantage under some conditions but sensitize the cells to oxidative stress. Intriguingly, relative to glioma cell lines, breast cancer cells have reduced levels of LTV1 and produce ribosomes lacking RPS3, RPS10, and RACK1. These data describe a mechanism to ensure RP assembly and demonstrate how cancer cells circumvent this mechanism to generate diverse ribosome populations that can promote survival under stress.
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DOI：
10.1083/jcb.201409056
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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