Skolkovo Institute of Science and Technology, Moscow, Russia.
Faculty of Chemistry, Moscow State University, Moscow, Russia.
Nat Commun. 2021 Apr 16;12(1):2300. doi: 10.1038/s41467-021-22549-7.
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.
核酸形成双链结构的能力对地球上所有的生命系统都是至关重要的。目前关于功能性 RNA 结构的知识集中在局部碱基对上。然而，交联和邻近连接实验表明，长距离 RNA 结构非常丰富。在这里，我们展示了迄今为止最完整的人类蛋白编码基因保守互补区（PCCRs）目录。PCCRs 倾向于发生在内含子中，抑制间隔外显子，并阻断隐蔽和无活性的剪接位点。PCCRs 的双链结构得到了降低的 icSHAPE 核苷酸可及性、高丰度的 RNA 编辑位点和频繁出现的分叉 eCLIP 峰的支持。含有 PCCRs 的内含子在 RNAPII 减速时表现出独特的剪接模式，这表明剪接广泛受到共转录 RNA 折叠的影响。PCCRs 内 3'端的富集提出了一个有趣的假设，即 RNA 折叠和剪接之间的偶联可能介导共转录过程中对过早的前体 mRNA 切割和多聚腺苷酸化的抑制。
