揭示复杂性:分析 DNA、RNA 和蛋白质相互作用的先进方法。

Advances in cancer research Pub Date : 2024-01-01 Epub Date: 2024-07-20 DOI:10.1016/bs.acr.2024.06.010
Maria Leonor Peixoto, Esha Madan
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引用次数: 0

摘要

探索核酸内部和核酸之间错综复杂的相互作用,以及核酸与蛋白质之间的相互作用,对于揭示引导癌症发生和发展的分子复杂性具有举足轻重的意义。为了研究这些相互作用,人们开发了一系列高度特异和灵敏的分子技术。特定技术的选择取决于相互作用的具体性质。通常情况下,研究人员会综合使用这些不同的技术,以全面、整体地了解涉及 DNA-DNA、RNA-RNA、DNA-RNA 或蛋白质-DNA/RNA 的分子间和分子内相互作用。对核酸构象的研究揭示了传统核酸构象之外的其他二级结构,这些二级结构对癌症的发病途径具有影响。癌症的突变热点往往位于容易采用这些替代结构的序列中,这凸显了研究基因组内和转录组内相互作用(尤其是突变背景下的相互作用)对于加深我们对肿瘤学的理解的重要性。除了这些分子内相互作用外,DNA 和 RNA 之间的相互作用还会形成 DNA:RNA 杂交体(称为 R 环),甚至 DNA:DNA:RNA 三重结构,两者都会影响生物过程,最终对癌症产生影响。蛋白质与核酸的相互作用是细胞的固有现象,在正常和病理情况下都至关重要。尤其是基因突变或单一氨基酸变异会改变蛋白质的结构、功能和结合亲和力,从而影响癌症的发展。因此,了解野生型(WT)和突变型(MT)基因、转录本和蛋白质之间的差异势在必行。本综述旨在总结研究核酸与蛋白质相互作用的常用方法和技术,重点介绍每种技术的最新进展和不同适应性。
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Unraveling the complexity: Advanced methods in analyzing DNA, RNA, and protein interactions.

Exploring the intricate interplay within and between nucleic acids, as well as their interactions with proteins, holds pivotal significance in unraveling the molecular complexities steering cancer initiation and progression. To investigate these interactions, a diverse array of highly specific and sensitive molecular techniques has been developed. The selection of a particular technique depends on the specific nature of the interactions. Typically, researchers employ an amalgamation of these different techniques to obtain a comprehensive and holistic understanding of inter- and intramolecular interactions involving DNA-DNA, RNA-RNA, DNA-RNA, or protein-DNA/RNA. Examining nucleic acid conformation reveals alternative secondary structures beyond conventional ones that have implications for cancer pathways. Mutational hotspots in cancer often lie within sequences prone to adopting these alternative structures, highlighting the importance of investigating intra-genomic and intra-transcriptomic interactions, especially in the context of mutations, to deepen our understanding of oncology. Beyond these intramolecular interactions, the interplay between DNA and RNA leads to formations like DNA:RNA hybrids (known as R-loops) or even DNA:DNA:RNA triplex structures, both influencing biological processes that ultimately impact cancer. Protein-nucleic acid interactions are intrinsic cellular phenomena crucial in both normal and pathological conditions. In particular, genetic mutations or single amino acid variations can alter a protein's structure, function, and binding affinity, thus influencing cancer progression. It is thus, imperative to understand the differences between wild-type (WT) and mutated (MT) genes, transcripts, and proteins. The review aims to summarize the frequently employed methods and techniques for investigating interactions involving nucleic acids and proteins, highlighting recent advancements and diverse adaptations of each technique.

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