ciRNAs

Circular intronic RNAs (ciRNAs) are a class of circular RNAs derived exclusively from intron sequences. They are produced when intron lariats generated during pre-mRNA splicing escape the usual debranching and degradation process, resulting in a covalently closed RNA molecule composed of intronic sequences only.

Biogenesis and features: After splicing, most introns are debranched and degraded by enzymes such as Dbr1. Some introns, however, harbor sequence elements that promote lariat persistence, notably a GU-rich region near the 5' splice site and a C-rich region around the branch point. These motifs help the lariat evade debranching and be processed into a stable circular RNA. Because they are entirely intronic, ciRNAs are typically localized to the nucleus and tend to be more stable than many linear RNAs.

Functions: ciRNAs have been proposed to regulate transcription of their parental genes in cis, by interacting with transcriptional machinery within the nucleus. This supports a role in modulating gene expression rather than acting as generic post-transcriptional regulators. Evidence for functional roles is still being developed, and the full set of mechanisms and biological contexts is an active area of research. Some ciRNAs have been linked to development and disease, but widely across tissues their prevalence and impact remain to be fully characterized.

Relation to other circRNAs: ciRNAs are distinct from exonic circRNAs and from exon–intron circRNAs (EIciRNAs) because they consist solely of intronic sequences. They are identified in RNA-seq data after ribosomal RNA depletion and validated by methods such as RT-PCR across back-splice junctions and RNase-resistant circularity.

History: The concept of ciRNAs emerged from studies of nuclear circRNAs that can influence host gene transcription, with subsequent discoveries expanding the catalog and proposed functions of this RNA class.