Phosphorylation of the Ribosomal Protein RPL12/uL11 Affects Translation during Mitosis
Phosphorylation of the Ribosomal Protein RPL12/uL11 Affects Translation during Mitosis
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DOI：
10.1016/j.molcel.2018.08.019
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发表时间：
2018-10-04
期刊：
影响因子：
16
通讯作者：
Selbach, Matthias
中科院分区：
文献类型：
--
作者：
Imami, Koshi;Milek, Miha;Selbach, Matthias
新出现的证据表明，核糖体组成的异质性可以产生专门的功能。到目前为止，研究主要集中在核心核糖体蛋白及其相关因子的差异上。翻译后修饰的作用尚未得到系统的研究。分析核糖体异质性具有挑战性，因为单个蛋白质可能是不同亚复合物（40S, 60S， 80S和多体）的一部分。在这里，我们开发了多体蛋白质组分析，以获得跨核糖体亚复合物的无偏蛋白质组图。本方法将蔗糖梯度离心广泛分离与定量质谱相结合。这些图谱的高分辨率使我们能够将蛋白质分配到特定的亚复合物上。磷酸化蛋白质组学显示，已知的有丝分裂CDK1底物RPL12/uL11中丝氨酸38的磷酸化在多体中强烈减少。后续实验证实，RPL12/uL11磷酸化调节有丝分裂过程中特定mrna亚群的翻译。总之，我们的研究结果表明，核糖体蛋白的翻译后修饰可以调节翻译。
Emerging evidence indicates that heterogeneity in ribosome composition can give rise to specialized functions. Until now, research mainly focused on differences in core ribosomal proteins and associated factors. The effect of posttranslational modifications has not been studied systematically. Analyzing ribosome heterogeneity is challenging because individual proteins can be part of different subcomplexes (40S, 60S, 80S, and polysomes). Here we develop polysome proteome profiling to obtain unbiased proteomic maps across ribosomal subcomplexes. Our method combines extensive fractionation by sucrose gradient centrifugation with quantitative mass spectrometry. The high resolution of the profiles allows us to assign proteins to specific subcomplexes. Phosphoproteomics on the fractions reveals that phosphorylation of serine 38 in RPL12/uL11, a known mitotic CDK1 substrate, is strongly depleted in polysomes. Follow-up experiments confirm that RPL12/uL11 phosphorylation regulates the translation of specific subsets of mRNAs during mitosis. Together, our results show that posttranslational modification of ribosomal proteins can regulate translation.