Fonseca Bruno D, Lahr Roni M, Damgaard Christian K, Alain Tommy, Berman Andrea J
Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Wiley Interdiscip Rev RNA. 2018 Sep;9(5):e1480. doi: 10.1002/wrna.1480. Epub 2018 May 2.
The ribosome is an essential unit of all living organisms that commands protein synthesis, ultimately fuelling cell growth (accumulation of cell mass) and cell proliferation (increase in cell number). The eukaryotic ribosome consists of 4 ribosomal RNAs (rRNAs) and 80 ribosomal proteins (RPs). Despite its fundamental role in every living organism, our present understanding of how higher eukaryotes produce the various ribosome components is incomplete. Uncovering the mechanisms utilized by human cells to generate functional ribosomes will likely have far-reaching implications in human disease. Recent biochemical and structural studies revealed La-related protein 1 (LARP1) as a key new player in RP production. LARP1 is an RNA-binding protein that belongs to the LARP superfamily; it controls the translation and stability of the mRNAs that encode RPs and translation factors, which are characterized by a 5' terminal oligopyrimidine (5'TOP) motif and are thus known as TOP mRNAs. The activity of LARP1 is regulated by the mammalian target of rapamycin complex 1 (mTORC1): a eukaryotic protein kinase complex that integrates nutrient sensing with mRNA translation, particularly that of TOP mRNAs. In this review, we provide an overview of the role of LARP1 in the control of ribosome production in multicellular eukaryotes. This article is categorized under: Translation > Translation Regulation RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Processing > Capping and 5' End Modifications.
核糖体是所有生物的基本组成部分,负责蛋白质合成,最终推动细胞生长(细胞质量的积累)和细胞增殖(细胞数量的增加)。真核核糖体由4种核糖体RNA(rRNA)和80种核糖体蛋白(RP)组成。尽管核糖体在每种生物中都起着至关重要的作用,但我们目前对高等真核生物如何产生各种核糖体成分的理解并不完整。揭示人类细胞用于生成功能性核糖体的机制可能会对人类疾病产生深远影响。最近的生化和结构研究表明,La相关蛋白1(LARP1)是核糖体蛋白产生过程中的一个关键新角色。LARP1是一种RNA结合蛋白,属于LARP超家族;它控制编码核糖体蛋白和翻译因子的mRNA的翻译和稳定性,这些mRNA的特征是具有5'末端寡嘧啶(5'TOP)基序,因此被称为TOP mRNA。LARP1的活性受雷帕霉素复合物1(mTORC1)的哺乳动物靶点调节:mTORC1是一种真核蛋白激酶复合物,它将营养感知与mRNA翻译整合在一起,特别是TOP mRNA的翻译。在这篇综述中,我们概述了LARP1在多细胞真核生物核糖体产生控制中的作用。本文分类如下:翻译>翻译调控;RNA与蛋白质和其他分子的相互作用>蛋白质-RNA相互作用:功能影响;RNA加工>加帽和5'末端修饰。