Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA
mSphere. 2019 Aug 21;4(4):e00475-19. doi: 10.1128/mSphere.00475-19.
Eukaryotic ribosome biogenesis is an essential cellular process involving tightly coordinated assembly of multiple rRNA and protein components. Much of our understanding of this pathway has come from studies performed with yeast model systems. These studies have identified critical checkpoints in the maturation of the large ribosomal subunit (LSU/60S), one of which is the proper formation and incorporation of the 5S ribonucleoprotein complex (5S RNP). Research on the 5S RNP has identified a complex containing the four proteins L5, L11, Rpf2, and Rrs1 as well as 5S rRNA. Our laboratory has studied the 5S RNP in , a eukaryotic parasite, and identified the proteins P34 and P37 as essential, parasite-specific members of this complex. We have additionally identified homologues of L5, Rpf2, Rrs1, and 5S rRNA in and characterized their roles in this essential process. In this study, we examined the homologue of ribosomal protein L11 as a member of the 5S RNP. We showed that TbL11 is essential and that it is important for proper ribosome subunit formation and 60S rRNA processing. Additionally, we identified TbL11 interactions with TbL5 and TbRpf2, as well as novel interactions with the kinetoplast-specific proteins P34 and P37. These findings expand our understanding of a crucial process outside the context of model yeast organisms and highlight differences in an otherwise highly conserved process that could be used to develop future treatments against The human-pathogenic, eukaryotic parasite causes human and animal African trypanosomiases. Treatments for suffer from numerous hurdles, including adverse side effects and developing resistance. Ribosome biogenesis is one critical process for survival that could be targeted for new drug development. A critical checkpoint in ribosome biogenesis is formation of the 5S RNP, which we have shown involves the trypanosome-specific proteins P34 and P37 as well as homologues of Rpf2, Rrs1, and L5. We have identified parasite-specific characteristics of these proteins and involvement in key parts of ribosome biogenesis, making them candidates for future drug development. In this work, we characterized the homologue of ribosomal protein L11. We show that it is essential for parasite survival and is involved in ribosome biogenesis and rRNA processing. Furthermore, we identified novel interactions with P34 and P37, characteristics that make this protein a potential target for novel chemotherapeutics.
真核生物核糖体生物发生是一个涉及多个 rRNA 和蛋白质成分紧密协调组装的基本细胞过程。我们对这一途径的认识很大程度上来自于酵母模型系统的研究。这些研究确定了大核糖体亚基（LSU/60S）成熟过程中的关键检查点，其中之一是 5S 核糖核蛋白复合物（5S RNP）的正确形成和掺入。对 5S RNP 的研究确定了一个包含四个蛋白质 L5、L11、Rpf2 和 Rrs1 以及 5S rRNA 的复合物。我们的实验室研究了真核寄生虫 中的 5S RNP，并确定了蛋白质 P34 和 P37 是该复合物中必不可少的寄生虫特异性成员。我们还鉴定了 中的 L5、Rpf2、Rrs1 和 5S rRNA 的同源物，并对它们在这个基本过程中的作用进行了表征。在这项研究中，我们研究了核糖体蛋白 L11 的同源物作为 5S RNP 的一个成员。我们表明，TbL11 是必不可少的，它对正确的核糖体亚基形成和 60S rRNA 加工很重要。此外，我们还鉴定了 TbL11 与 TbL5 和 TbRpf2 的相互作用，以及与动基体特异性蛋白 P34 和 P37 的新相互作用。这些发现扩展了我们对模型酵母生物体外一个关键过程的理解，并强调了一个高度保守过程中的差异，这些差异可用于开发针对 的未来治疗方法。人类致病的真核寄生虫 引起人类和动物的非洲锥虫病。针对 的治疗方法存在许多障碍，包括不良反应和耐药性的产生。核糖体生物发生是 生存的一个关键过程，可能成为新药开发的目标。核糖体生物发生的一个关键检查点是 5S RNP 的形成，我们已经表明，这涉及到锥虫特异性蛋白 P34 和 P37 以及 Rpf2、Rrs1 和 L5 的同源物。我们已经确定了这些蛋白质的寄生虫特异性特征，并参与了核糖体生物发生和 rRNA 加工的关键部分，使它们成为未来药物开发的候选者。在这项工作中，我们对核糖体蛋白 L11 的同源物进行了表征。我们表明，它对寄生虫的生存是必不可少的，并且参与了核糖体生物发生和 rRNA 加工。此外，我们还鉴定了与 P34 和 P37 的新相互作用，这些特性使该蛋白成为新型化学疗法的潜在靶标。
