Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, United States.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, United States.
Adv Clin Chem. 2021;100:1-35. doi: 10.1016/bs.acc.2020.04.001. Epub 2020 May 27.
Chimeric RNAs are hybrid transcripts containing exons from two separate genes. Chimeric RNAs are traditionally considered to be transcribed from fusion genes caused by chromosomal rearrangement. These canonical chimeric RNAs are well characterized to be expressed in a cancer-unique pattern and/or act as oncogene products. However, benefited by the development of advanced deep sequencing technologies, novel types of non-canonical chimeric RNAs have been discovered to be generated from intergenic splicing without genomic aberrations. They can be formed through trans-splicing or cis-splicing between adjacent genes (cis-SAGe) mechanisms. Non-canonical chimeric RNAs are widely detected in normal physiology, although several have been shown to have a cancer-specific expression pattern. Further studies have indicated that some of them play fundamental roles in controlling cell growth and motility, and may have functions independent of the parental genes. These discoveries are unveiling a new layer of the functional transcriptome and are also raising the possibility of utilizing non-canonical chimeric RNAs as cancer diagnostic markers and therapeutic targets. In this chapter, we will overview different categories of chimeric RNAs and their expression in various types of cancerous and normal samples. Acknowledging that chimeric RNAs are not unique to cancer, we will discuss both bioinformatic and biological methods to identify credible cancer-specific chimeric RNAs. Furthermore, we will describe downstream methods to explore their molecular processing mechanisms and potential functions. A better understanding of the biogenesis mechanisms and functional products of cancer-specific chimeric RNAs will pave ways for the development of novel cancer biomarkers and therapeutic targets.
嵌合 RNA 是一种含有两个不同基因外显子的杂交转录本。传统上，嵌合 RNA 被认为是由染色体重排引起的融合基因转录而来的。这些典型的嵌合 RNA 具有独特的癌症表达模式，并/或作为癌基因产物。然而，得益于先进的深度测序技术的发展，已经发现了新型非典型嵌合 RNA，它们是通过基因间剪接产生的，而没有基因组异常。它们可以通过相邻基因之间的反式剪接(trans-splicing)或顺式剪接(cis-splicing)（顺式 SAGe）机制形成。非典型嵌合 RNA 在正常生理中广泛存在，尽管已经发现其中一些具有特定的癌症表达模式。进一步的研究表明，其中一些在控制细胞生长和运动中发挥着重要作用，并且可能具有与亲本基因无关的功能。这些发现揭示了功能转录组的一个新层次，也提高了将非典型嵌合 RNA 用作癌症诊断标志物和治疗靶点的可能性。在本章中，我们将概述不同类别的嵌合 RNA 及其在各种类型的癌症和正常样本中的表达。鉴于嵌合 RNA 并非癌症所特有，我们将讨论用于识别可信的癌症特异性嵌合 RNA 的生物信息学和生物学方法。此外，我们将描述下游方法来探索它们的分子加工机制和潜在功能。更好地了解癌症特异性嵌合 RNA 的生物发生机制和功能产物将为开发新型癌症生物标志物和治疗靶点铺平道路。
