circRNA

CircRNA, or circular RNA, is a covalently closed RNA molecule formed when a downstream 5' splice site joins an upstream 3' splice site, creating a back-splice junction. Unlike linear mRNAs, circRNAs lack 5' caps and 3' poly(A) tails, are resistant to exonucleases, and are generally more stable in cells. They are expressed in a cell-type and tissue-specific manner and can accumulate with age.

Biogenesis occurs through back-splicing; major classes include exonic circRNAs (ecircRNAs), circular intronic RNAs (ciRNAs), and exon-intron circRNAs (EIciRNAs). Formation is promoted by complementary intronic sequences and RNA-binding proteins such as QKI, MBL, FUS; the spliceosome participates. Most circRNAs localize to cytoplasm; EIciRNA/ciRNA often nuclear and can regulate transcription of their parental genes.

Functions include acting as microRNA sponges, binding RBPs, and modulating gene expression. Some circRNAs harbor open reading frames and can be translated via IRES or m6A-driven mechanisms, producing short peptides. They also may influence splicing of linear transcripts or serve as scaffolds for protein complexes. CircRNAs can be released in extracellular vesicles, enabling intercellular communication.

Detection and study: identified by sequencing reads that span back-splice junctions; enrichment by RNase R; challenging to distinguish from linear transcripts; validation by qRT-PCR across junctions, Northern blot, or RNase protection. Clinically, circRNAs are explored as biomarkers due to stability in body fluids; altered circRNA expression has been linked to cancers, neurological diseases, and cardiovascular disorders.