backspliced

Backspliced refers to the products and processes of back-splicing, a noncanonical RNA splicing event in eukaryotic pre-mRNA in which a downstream 5' splice donor site is joined to an upstream 3' splice acceptor site. The result is a covalently closed circular RNA molecule that lacks free ends and contains a backsplice junction, often formed from exons or intron sequences.

Biogenesis of backspliced RNAs involves two main models. In lariat-driven circularization, exon skipping creates a lariat containing exons that is processed into a circular RNA. In intron pairing-driven circularization, complementary sequences in flanking introns base pair to bring the splice sites into proximity, with RNA-binding proteins further facilitating the reaction. These processes yield circRNAs that can include only exons (ecircRNAs), exons with retained introns (EIciRNAs), or intron-derived circRNAs (ciRNAs).

Types and features of backspliced products reflect their composition. EcircRNAs are composed predominantly of exons; EIciRNAs retain intronic sequences and may localize to the nucleus, where they can influence transcription; ciRNAs arise primarily from intron sequences. The precise function of individual circRNAs is diverse and context-dependent.

Functional significance is broad but not uniform across circRNAs. Many act as microRNA sponges or bind RNA-binding proteins, thereby modulating gene expression and protein interactions. Some circRNAs can be translated if they contain an internal ribosome entry site or other translation signals. Their circular structure confers increased stability relative to linear RNAs, and they are detectable across plants and animals, with tissue- and development-specific expression patterns.

Detection and study rely on high-throughput sequencing to identify backsplice junctions, supported by computational tools and experimental validation (for example, RT-PCR across the backsplice junction and RNase R treatment to enrich circular species).