Global Mapping of Human RNA-RNA Interactions

The majority of the human genome is transcribed into non-coding (nc)RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing, modification, turnover, and translation. To define roles for ncRNAs, we have developed a method enabling the global-scale mapping of RNA-RNA duplexes crosslinked in vivo, “LIGation of interacting RNA followed by high-throughput sequencing” (LIGR-seq). Applying this method in human cells reveals a remarkable landscape of RNA-RNA interactions involving all major classes of ncRNA and mRNA. LIGR-seq data reveal unexpected interactions between small nucleolar (sno)RNAs and mRNAs, including those involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions. [Display omitted] •LIGR-seq is a method for the global-scale mapping RNA-RNA interactions in vivo•LIGR-seq data reveal a complex RNA-RNA interactome in human cells•Hundreds of trans-interactions involving known and orphan ncRNAs are detected•The orphan snoRNA SNORD83B regulates levels of its LIGR-seq-detected target mRNAs Most non-coding RNAs lack known functions or else are poorly characterized. Sharma, Sterne-Weiler et al. describe “LIGation of interacting RNA and high-throughput sequencing” (LIGR-seq), a method for the global-scale mapping of RNA-RNA interactions in vivo. Mapping the RNA-RNA interactome in human cells reveals unexpected functions for small nucleolar RNAs.