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Introns encode a vast class of Kink-loop RNAs that autoregulate pre-mRNA splicing

Created on 05 Aug 2026

Authors

Li, B., Lin, Q., Liu, A., Gan, H., Liu, S., Zheng, W., Liang, Y., Wan, G., Qu, L., Yang, J.

Abstract

Introns occupy nearly one-third of the human genome, yet whether they encode widespread regulatory functions remains unclear. Here, we identify a pervasive class of intron-derived Kink-loop RNAs (klRNAs) that locally control pre-mRNA processing. Using complementary enrichment strategies, we uncovered approximately 15,200 and 3,500 previously unannotated klRNAs in humans and mice, respectively. Bound by the conserved RNA-binding protein 15.5K, klRNAs constitute a distinct family of structured RNAs that arise predominantly from introns, lack the canonical stems of Kink-turn motifs, and do not exhibit antisense complementarity to known non-coding RNAs. Depletion of 15.5K disrupts klRNA biogenesis and leads to their global loss. Transcriptome-wide analyses reveal that klRNAs function predominantly in cis to suppress excision of their host introns in a kink-loop structure-dependent manner, thereby enabling introns to regulate their own processing. Together, our findings establish RNA structure-encoded autoregulation as a pervasive mechanism controlling intron fate and reveal that introns are active sources of regulatory RNAs.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Aug 2026.

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