Global mapping of circRNA-target RNA interactions reveal P-body-mediated translational repression

Molecular Cell, 16 February, 2026, DOI：https://doi.org/10.1016/j.molcel.2026.01.018

Global mapping of circRNA-target RNA interactions reveal P-body-mediated translational repression

Peng Li, Hongmei Zhang, Zhaokui Cai, Yuyang Zhang, Ruiyun Yang, Rong Ye, Jingxin Li, Hailian Zhao, Bowen Liu, Zhen Yuan, Xuekun Li, Xi Wang, Ping Zhu, Yuanchao Xue

Abstract

Circular RNAs (circRNAs) are primarily produced through pre-mRNA back-splicing, yet their target repertoire and functional mechanisms remain elusive. Here, we present circTargetMap, a computational framework for globally mapping circRNA targets using RNA-RNA interactomes obtained via RNA in situ conformation sequencing (RIC-seq) in the hippocampus and ten human cell lines. This approach identified 117,163 high-confidence circRNA-target RNA interactions, with 83% of target mRNAs bound by multiple circRNAs. Functionally, CDR1as and circRMST repress target mRNA translation by sequestering them into processing bodies (P-bodies)—membraneless granules—through sequence-specific base-pairing, probably independent of AGO2, DICER, and microRNA (miRNAs). To directly capture granule-associated interactions, we developed the granule RIC-seq (GRIC-seq) method, revealing the broad role of circRNA-target RNA interactions in translational repression. Moreover, pathogenic variants are significantly enriched around circRNA-target RNA interaction sites, suggesting potential roles in disease. Our study provides valuable resources for circRNA functional exploration and a framework for investigating RNA-RNA interactions within membraneless organelles.

文章链接：https://www.sciencedirect.com/science/article/pii/S1097276526000389?via%3Dihub