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

ABSTRACT

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.