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癌症生物学家为何要关注转运RNA(tRNA)?tRNA合成、信使核糖核酸(mRNA)翻译与生长调控。

Why should cancer biologists care about tRNAs? tRNA synthesis, mRNA translation and the control of growth.

作者信息

Grewal Savraj S

机构信息

Department of Biochemistry and Molecular Biology, Clark H. Smith Brain Tumour Centre, Southern Alberta Cancer Research Institute, University of Calgary, HRIC, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.

出版信息

Biochim Biophys Acta. 2015 Jul;1849(7):898-907. doi: 10.1016/j.bbagrm.2014.12.005. Epub 2014 Dec 11.

Abstract

Transfer RNAs (tRNAs) are essential for mRNA translation. They are transcribed in the nucleus by RNA polymerase III and undergo many modifications before contributing to cytoplasmic protein synthesis. In this review I highlight our understanding of how tRNA biology may be linked to the regulation of mRNA translation, growth and tumorigenesis. First, I review how oncogenes and tumour suppressor signalling pathways, such as the PI3 kinase/TORC1, Ras/ERK, Myc, p53 and Rb pathways, regulate Pol III and tRNA synthesis. In several cases, this regulation contributes to cell, tissue and body growth, and has implications for our understanding of tumorigenesis. Second, I highlight some recent work, particularly in model organisms such as yeast and Drosophila, that shows how alterations in tRNA synthesis may be not only necessary, but also sufficient to drive changes in mRNA translation and growth. These effects may arise due to both absolute increases in total tRNA levels, but also changes in the relative levels of tRNAs in the overall pool. Finally, I review some recent studies that have revealed how tRNA modifications (amino acid acylation, base modifications, subcellular shuttling, and cleavage) can be regulated by growth and stress cues to selectively influence mRNA translation. Together these studies emphasize the importance of the regulation of tRNA synthesis and modification as critical control points in protein synthesis and growth. This article is part of a Special Issue entitled: Translation and Cancer.

摘要

转运RNA(tRNA)对于mRNA翻译至关重要。它们由RNA聚合酶III在细胞核中转录而成,并在参与细胞质蛋白质合成之前经历许多修饰。在这篇综述中,我着重介绍了我们对于tRNA生物学如何与mRNA翻译、生长及肿瘤发生的调控相联系的理解。首先,我回顾了癌基因和肿瘤抑制信号通路,如PI3激酶/TORC1、Ras/ERK、Myc、p53和Rb通路,如何调控RNA聚合酶III和tRNA合成。在一些情况下,这种调控有助于细胞、组织和机体生长,并对我们理解肿瘤发生有重要意义。其次,我强调了一些近期的研究工作,特别是在酵母和果蝇等模式生物中的研究,这些研究表明tRNA合成的改变不仅可能是驱动mRNA翻译和生长变化所必需的,而且也是充分的。这些效应可能是由于tRNA总量的绝对增加,也可能是由于整个tRNA库中tRNA相对水平的变化。最后,我回顾了一些近期的研究,这些研究揭示了tRNA修饰(氨基酸酰化、碱基修饰、亚细胞穿梭和切割)如何受生长和应激信号的调控,从而选择性地影响mRNA翻译。这些研究共同强调了tRNA合成和修饰的调控作为蛋白质合成和生长关键控制点的重要性。本文是名为“翻译与癌症”的特刊的一部分。

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