The ‘Not-So-Famous Five’ in tumorigenesis: tRNAs, tRNA fragments, and tRNA epitranscriptome in concert with AARSs and AIMPs

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Sutapa Saha , Biyas Mukherjee , Proma Banerjee , Debadrita Das
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Abstract

RNA profiling studies have revealed that ∼75% of the human genome is transcribed to RNA but only a meagre fraction of it is translated to proteins. Majority of transcribed RNA constitute a specialized pool of non-coding RNAs. Human genome contains approximately 506 genes encoding a set of 51 different tRNAs, constituting a unique class of non-coding RNAs that not only have essential housekeeping functions as translator molecules during protein synthesis, but have numerous uncharted regulatory functions. Intriguing findings regarding a variety of non-canonical functions of tRNAs, tRNA derived fragments (tRFs), esoteric epitranscriptomic modifications of tRNAs, along with aminoacyl-tRNA synthetases (AARSs) and ARS-interacting multifunctional proteins (AIMPs), envision a ‘peripheral dogma’ controlling the flow of genetic information in the backdrop of qualitative information wrung out of the long-live central dogma of molecular biology, to drive cells towards either proliferation or differentiation programs. Our review will substantiate intriguing peculiarities of tRNA gene clusters, atypical tRNA-transcription from internal promoters catalysed by another distinct RNA polymerase enzyme, dynamically diverse tRNA epitranscriptome, intricate mechanism of tRNA-charging by AARSs governing translation fidelity, epigenetic regulation of gene expression by tRNA fragments, and the role of tRNAs and tRNA derived/associated molecules as quantitative determinants of the functional proteome, covertly orchestrating the process of tumorigenesis, through a deregulated tRNA-ome mediating selective codon-biased translation of cancer related gene transcripts.

Abstract Image

肿瘤发生过程中的 "非著名五人组":tRNAs、tRNA 片段、tRNA 表转录组与 AARSs 和 AIMPs 的协同作用。
RNA 分析研究显示,人类基因组中有 75% 的 RNA 被转录为 RNA,但只有很少一部分被翻译成蛋白质。大部分转录 RNA 构成了一个专门的非编码 RNA 库。人类基因组包含约 506 个基因,编码 51 种不同的 tRNA,构成了一类独特的非编码 RNA,它们不仅在蛋白质合成过程中作为翻译分子发挥着重要的内务功能,还具有许多未知的调控功能。有关 tRNAs、tRNA 衍生片段(tRFs)、tRNAs 的深奥表转录组修饰以及氨基酰-tRNA 合成酶(AARSs)和 ARS 相互作用多功能蛋白(AIMPs)的各种非规范功能的研究结果引人入胜、在从分子生物学长期存在的中心教条中提炼出的定性信息的背景下,"外围教条 "控制着遗传信息的流动,从而推动细胞走向增殖或分化程序。我们的综述将证实 tRNA 基因簇的奇特之处、由另一种不同的 RNA 聚合酶催化的来自内部启动子的非典型 tRNA 转录、动态多样的 tRNA 表转录组、由 AARSs 控制翻译保真度的 tRNA 充电的复杂机制、tRNA 片段对基因表达的表观遗传调控,以及 tRNA 和 tRNA 衍生/相关分子作为功能蛋白质组定量决定因素的作用,通过失调的 tRNA 组介导癌症相关基因转录本的选择性密码子偏向翻译,暗中协调肿瘤发生过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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