Detection and Validation of Chimeric RNA / 生物化学与生物物理进展

Chimeric RNA is a fusion transcript comprising of exon fragments from different genes. There are three splicing types: chromosome rearrangements, trans-splicing, cis-splicing, and the recently mentioned circular chimeric RNA. The traditional methods for the detection of chimeric RNA includes chromosome karyotype analysis, FISH, DNA microarray, etc., but their specificity, sensitivity and accuracy for the detection of chimeric RNA are poorly understood. With the development of sequencing technology, second-generation sequencing technology has shown strong data processing capabilities and can detect chimeric RNA through high-throughput sequence analysis. Currently, detection methods making use of high-throughput sequencing datasets includes FusionCatcher, SOAPfuse, EricScript, etc. For validation of the detected chimeric RNA, the commonly used methods include PCR, RPA, agarose gel electrophoresis, sanger sequencing, etc. The development of newly introduced techniques has led to the discovery of different novel chimeric RNA, the third and fourth generation sequencing has also been developed and nearly mature, and the sequencing technology taking PacBio as an example has also brought a new dawn to the discovery of chimeric RNA, but each of them has its advantages and disadvantages, mainly focusing on its cost, false positive rate, detection time, etc. This paper basically describes various different techniques that can be utilized for the detection and validation of chimeric RNA.

Biological Implication of Chimeric RNAs in Cancer / 中国生物化学与分子生物学报

Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.

The Formation Mechanism and Functional Implication of Chimeric RNAs / 中国生物化学与分子生物学报

Traditionally, chimeric RNA is thought to be generated by chromosome rearrangement, and its products (RNAs and proteins) were once considered as unique features of cancer. However, with the advancement of next-generation sequencing technologies and the development of bioinformatics software tools, increasing numbers of chimeric RNAs are being identified from various RNA-Seq database. Recently, numerous chimeric RNAs were discovered in human normal tissues and cell lines, with physiological functions. Besides chromosome rearrangement, chimeric RNAs are formed by different molecular mechanisms, including trans-splicing, cis-splicing of adjacent genes. Chimeric RNAs, without chromosomal changes, are regulated at the transcriptional level, and they show specific physiological functions and regulation patterns. Their dysregulation may induce cell differentiation and tumorogenisis. In addition, chimeric RNAs also play roles in normal cell growth and/or migration, cell cycle and apoptosis, induce genomic aberration by influencing chromosome rearrangement, act as potential competitive endogenous RNA, and influence stem cell differentiation. The expression of chimeric RNAs in specific tissues and cell development stages has the potential to be used as diagnostic and therapeutic biomarkers. Histological mapping studies can improve the specificity of treatment for unique cell types, and the chimeric RNA provides a new perspective to achieve this goal. The widespread existence of chimeric RNAs suggests that they may extend the diversity of genomes in human and higher animals.