ADARS REGULATE ALTERNATIVE SPLICING AND BACKSPLICING

Abstract

The human transcriptome is greatly expanded by co- or post-transcriptional processing such as adenosine-to-inosine (A-to-I) RNA editing which changes the genetic code at RNA level, alternative splicing (AS) which produces multiple functional linear RNAs, and a more recently uncovered process-backsplicing which generates circular RNAs (circRNAs). Although dysregulation of these RNA processing steps has been linked to tumorigenesis in many cancer types, it remains unclear how they interplay with each other in the context of cancer. In sum, the findings from my PhD projects suggest that A-to-I RNA editing enzymes ADAR proteins can cross-regulate other RNA processing steps including alternative splicing and backsplicing, through its editing-dependent and/or -independent functions. The existence of transcripts resulting from crosstalk between editing enzymes and splicing machineries increases the complexity of transcriptome, and aberrantly regulated crosstalk events may contribute to human diseases such as cancer.