KARR-seq is a novel method that uses N3-kethoxal labeling and multifunctional chemical crosslinkers to covalently trap and determine RNA–RNA interactions and higher-order RNA structures inside cells, independent of local protein binding to RNA. This method accurately reveals RNA tertiary structures and identifies widespread intermolecular RNA–RNA interactions with high sensitivity and accuracy. Using KARR-seq, the authors show that translation represses mRNA compaction under native and stress conditions. They also determine the higher-order RNA structures of respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) and identify RNA–RNA interactions between the viruses and host RNAs that potentially regulate viral replication. KARR-seq enables precise and sensitive mapping of RNA–RNA interactions and RNA structurome, providing insights into RNA functions. The method is effective in capturing spatially proximal RNAs and can be applied to study RNA–RNA interactions in different cellular compartments, such as the nucleus and cytoplasm.KARR-seq is a novel method that uses N3-kethoxal labeling and multifunctional chemical crosslinkers to covalently trap and determine RNA–RNA interactions and higher-order RNA structures inside cells, independent of local protein binding to RNA. This method accurately reveals RNA tertiary structures and identifies widespread intermolecular RNA–RNA interactions with high sensitivity and accuracy. Using KARR-seq, the authors show that translation represses mRNA compaction under native and stress conditions. They also determine the higher-order RNA structures of respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) and identify RNA–RNA interactions between the viruses and host RNAs that potentially regulate viral replication. KARR-seq enables precise and sensitive mapping of RNA–RNA interactions and RNA structurome, providing insights into RNA functions. The method is effective in capturing spatially proximal RNAs and can be applied to study RNA–RNA interactions in different cellular compartments, such as the nucleus and cytoplasm.