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

Nat Commun. 2021 Apr 16;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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Base Pairing / physiology*
  • Base Sequence / genetics
  • Conserved Sequence / physiology
  • DNA, Complementary / genetics*
  • Gene Library
  • Hep G2 Cells
  • Humans
  • Introns / genetics
  • Polyadenylation
  • RNA Folding / physiology
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Splicing / physiology*
  • RNA-Seq

Substances

  • DNA, Complementary
  • RNA Precursors