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

Svetlana Kalmykova, Marina Kalinina, Stepan Denisov, Alexey Mironov, Dmitry Skvortsov, Roderic Guigó, Dmitri Pervouchine

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number2300
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

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