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 and Dmitri Pervouchine ()
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Svetlana Kalmykova: Skolkovo Institute of Science and Technology
Marina Kalinina: Skolkovo Institute of Science and Technology
Stepan Denisov: Skolkovo Institute of Science and Technology
Alexey Mironov: Skolkovo Institute of Science and Technology
Dmitry Skvortsov: Moscow State University
Roderic Guigó: Center for Genomic Regulation and UPF
Dmitri Pervouchine: Skolkovo Institute of Science and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22549-7

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DOI: 10.1038/s41467-021-22549-7

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