Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples. We generated RPL39L knock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread autophagy. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.

中文翻译：

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核糖体蛋白 RPL39L 是具有 α 螺旋结构域的蛋白质子集共翻译折叠的效率因子


越来越多的研究揭示了如何调整核糖体组成以最佳地翻译单个细胞类型的转录组。在本研究中，我们研究了核糖体蛋白旁系同源物 39L (RPL39L) 的表达模式、核糖体内结构以及对蛋白质合成的影响。通过一种新颖的质谱方法，我们揭示了 RPL39L 蛋白在小鼠生殖细胞之外、人类多能细胞、癌细胞系和组织样本中的表达。我们生成了 RPL39L 敲除小鼠胚胎干细胞 (mESC) 系，并证明 RPL39L 影响翻译动力学，以支持自发的和沿生殖细胞谱系的多能性和分化。 WT 和 RPL39L KO 系之间蛋白质丰度的大部分差异可以通过广泛的自噬来解释。通过对纯化的 RPL39 和含有 RPL39L 的核糖体进行 CryoEM 分析，我们发现，与 RPL39 不同，RPL39L 在新生肽出口通道的暴露片段中具有两种不同的构象，形成了一个独特的疏水性斑块，预计该斑块将支持有效的共翻译α螺旋的折叠。我们的研究表明，核糖体蛋白旁系同源物提供可切换的模块化组件，可以根据单个细胞类型的蛋白质生产需求调整翻译。