Fig. 4: KARR-seq identifies functional RNA–RNA interactions between diverse RNA categories.

a, The landscape of intermolecular RNA–RNA interactions revealed by KARR-seq in K562 cells (left) and K562 nucleus (right). The width of the link between two RNA categories denotes the relative abundance of chimeric reads taken by interactions between these two categories. mRNA–rRNA interactions, which are primarily a result of translation, were excluded from the plots. b, Interactions between C/D box snoRNA and 18S in K562 cells. Previously identified interaction sites are shown in pink. Interaction sites identified by KARR-seq are shown in green. c, Snapshots of KARR-seq data revealing SNORD25–18S and SNORD65–18S interactions. Regions colored in green denote identified interaction regions. The dashed lines denote previously known 2′ OMe modification sites. d, Scheme showing the organization and processing of human pre-rRNA 5′ ETS. e, Top, KARR-seq reads density for interactions between U3 and 5′ ETS in K562 cells (human) and mESCs (mouse). Bottom, KARR-seq interaction maps showing the higher-order structures of 5′ ETS in the corresponding cell lines. Stem loops are enclosed in black squares. f, Relative pre-rRNA levels in K562 cells treated by ASO that blocks a U3 interaction site at the 5′ ETS. Two sets of primers amplifying A′ and A0-proximal regions were applied for qPCR, respectively. Data are mean ± s.d. P values were calculated by Student’s t-test. n = 3 biological replicates. KARR-seq was performed in two biological replicates.