Conserved long-range base pairings are associated with pre-mRNA processing of human genes

Kalmykova, Svetlana; Kalinina, Marina; Denisov, Stepan; Mironov, Alexey; Skvortsov, Dmitry; Guigó Serra, Roderic; Pervouchine, Dmitri D.

doi:http://dx.doi.org/10.1038/s41467-021-22549-7

Conserved long-range base pairings are associated with pre-mRNA processing of human genes

License

Citation

Kalmykova S, Kalinina M, Denisov S, Mironov A, Skvortsov D, Guigó R, Pervouchine D. Conserved long-range base pairings are associated with pre-mRNA processing of human genes. Nat Commun. 2021;12(1):2300. DOI: 10.1038/s41467-021-22549-7

Abstract

The ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3'-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation.