1. Academic Validation
  2. RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators

RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators

  • Nat Biotechnol. 2023 Apr 10. doi: 10.1038/s41587-023-01749-0.
Bin Li # 1 Shurong Liu # 1 Wujian Zheng # 1 2 Anrui Liu # 1 2 Peng Yu # 1 Di Wu 1 2 Jie Zhou 1 2 Ping Zhang 1 Chang Liu 1 Qiao Lin 1 2 Jiayi Ye 1 2 Simeng He 2 Qiaojuan Huang 1 Hui Zhou 1 Jianjun Chen 3 Lianghu Qu 4 Jianhua Yang 5 6
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • 2 The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • 3 Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, USA.
  • 4 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. lssqlh@mail.sysu.edu.cn.
  • 5 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. yangjh7@mail.sysu.edu.cn.
  • 6 The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China. yangjh7@mail.sysu.edu.cn.
  • # Contributed equally.
Abstract

A kink-turn (K-turn) is a three-dimensional RNA structure that exists in all three primary phylogenetic domains. In this study, we developed the RIP-PEN-seq method to identify the full-length sequences of RNAs bound by the K-turn binding protein 15.5K and discovered a previously uncharacterized class of RNAs with backward K-turn motifs (bktRNAs) in humans and mice. All bktRNAs share two consensus sequence motifs at their fixed terminal position and have complex folding properties, expression and evolution patterns. We found that a highly conserved bktRNA1 guides the methyltransferase fibrillarin to install RNA methylation of U12 small nuclear RNA in humans. Depletion of bktRNA1 causes global splicing dysregulation of U12-type introns by impairing the recruitment of ZCRB1 to the minor spliceosome. Most bktRNAs regulate the splicing of local introns by interacting with the 15.5K protein. Taken together, our findings characterize a class of small RNAs and uncover another layer of gene expression regulation that involves crosstalk among bktRNAs, RNA splicing and RNA methylation.

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