Introns encode a vast new class of Kink-loop RNAs that autoregulate pre-mRNA splicing
- 1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes,
Abstract
Introns occupy nearly one-third of the human genome, yet whether they encode widespread regulatory functions remains unclear. Here, we identify a vast new class of intron-derived Kink-loop RNAs (klRNAs) that autoregulate host pre-mRNA splicing. We developed orthogonal sequencing methods to systematically uncover approximately 15,200 and 3,500 previously unannotated klRNAs in humans and mice, respectively. Bound by the conserved RNA-binding protein 15.5K, klRNAs are compact orphan RNAs characterized by stereotypically positioned terminal C/D motifs that form K-loop structures. Depletion of 15.5K broadly disrupts klRNA biogenesis. Functional and genetic perturbations establish that klRNAs suppress host intron excision through a K-loop-dependent mechanism. Together, our findings establish klRNA-mediated autoregulation as a widespread principle governing intron fate and reveal a previously unrecognized regulatory layer encoded within mammalian introns.
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BibTeX
@misc{li2026introns,
title = {{Introns encode a vast new class of Kink-loop RNAs that autoregulate pre-mRNA splicing}},
author = {B. Li and Q. Lin and A. Liu and H. Gan and S. Liu and W. Zheng and Y. Liang and G. Wan and L. Qu and J. Yang},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.03.742641},
url = {https://www.biorxiv.org/content/10.64898/2026.08.03.742641v2},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Introns encode a vast new class of Kink-loop RNAs that autoregulate pre-mRNA splicing
AU - B. Li
AU - Q. Lin
AU - A. Liu
AU - H. Gan
AU - S. Liu
AU - W. Zheng
AU - Y. Liang
AU - G. Wan
AU - L. Qu
AU - J. Yang
PY - 2026
DA - 2026/08/03
PB - bioRxiv
DO - 10.64898/2026.08.03.742641
UR - https://www.biorxiv.org/content/10.64898/2026.08.03.742641v2
AB - Introns occupy nearly one-third of the human genome, yet whether they encode widespread regulatory functions remains unclear. Here, we identify a vast new class of intron-derived Kink-loop RNAs (klRNAs) that autoregulate host pre-mRNA splicing. We developed orthogonal sequencing methods to systematically uncover approximately 15,200 and 3,500 previously unannotated klRNAs in humans and mice, respectively. Bound by the conserved RNA-binding protein 15.5K, klRNAs are compact orphan RNAs characterized by stereotypically positioned terminal C/D motifs that form K-loop structures. Depletion of 15.5K broadly disrupts klRNA biogenesis. Functional and genetic perturbations establish that klRNAs suppress host intron excision through a K-loop-dependent mechanism. Together, our findings establish klRNA-mediated autoregulation as a widespread principle governing intron fate and reveal a previously unrecognized regulatory layer encoded within mammalian introns.
ER -