Advances in detecting N6-methyladenosine modification in circRNAs.

Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently single-stranded closed loop structures derived from back-splicing event of linear precursor mRNAs (pre-mRNAs). N6-methyladenosine (mA), the most abundant epigenetic modification in eukaryotic RNAs, has been shown to play a crucial role in regulating the fate and biological function of circRNAs, and thus affecting various physiological and pathological processes. Accurate identification of mA modification in circRNAs is an essential step to fully elucidate the crosstalk between mA and circRNAs. In recent years, the rapid development of high-throughput sequencing technology and bioinformatic methodology has propelled the establishment of a multitude of approaches to detect circRNAs and mA modification, including in vitro-based and in silico methods. Based on this, the research community has started on a new journey to develop methods for identification of mA modification in circRNAs. In this review, we provide a comprehensive review and evaluation of the existing methods responsible for detecting circRNAs, mA modification, and especially, mA modification in circRNAs, which mainly focused on those developed based on high-throughput technologies and methodology of bioinformatics. This handy reference can help researchers figure out towards which direction this field will go.