RIC-seq for global in situ profiling of RNA-RNA spatial interactions.
IF: 69.504
Cited by: 141


Highly structured RNA molecules usually interact with each other, and associate with various RNA-binding proteins, to regulate critical biological processes. However, RNA structures and interactions in intact cells remain largely unknown. Here, by coupling proximity ligation mediated by RNA-binding proteins with deep sequencing, we report an RNA in situ conformation sequencing (RIC-seq) technology for the global profiling of intra- and intermolecular RNA-RNA interactions. This technique not only recapitulates known RNA secondary structures and tertiary interactions, but also facilitates the generation of three-dimensional (3D) interaction maps of RNA in human cells. Using these maps, we identify noncoding RNA targets globally, and discern RNA topological domains and trans-interacting hubs. We reveal that the functional connectivity of enhancers and promoters can be assigned using their pairwise-interacting RNAs. Furthermore, we show that CCAT1-5L-a super-enhancer hub RNA-interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Our study demonstrates the power and applicability of RIC-seq in discovering the 3D structures, interactions and regulatory roles of RNA.



MeSH terms

Cell Line
Chromosomes, Human
Enhancer Elements, Genetic
Genes, myc
Genes, rRNA
Heterogeneous-Nuclear Ribonucleoprotein K
Nucleic Acid Conformation
Promoter Regions, Genetic
RNA, Long Noncoding
Reproducibility of Results
Sequence Analysis, RNA
Transcription, Genetic


Cai, Zhaokui
Cao, Changchang
Ji, Lei
Ye, Rong
Wang, Di
Xia, Cong
Wang, Sui
Du, Zongchang
Hu, Naijing
Yu, Xiaohua
Chen, Juan
Wang, Lei
Yang, Xianguang
He, Shunmin
Xue, Yuanchao

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