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

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sutapa Saha , Biyas Mukherjee , Proma Banerjee , Debadrita Das
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引用次数: 0

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
Biochimie
Biochimie 生物-生化与分子生物学
CiteScore
7.20
自引率
2.60%
发文量
219
审稿时长
40 days
期刊介绍: Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English. Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.
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