Global mapping of RNA homodimers in living cells

RNA homodimerization is important for various physiological processes,
including the assembly of membraneless organelles, RNA subcellular
localization, and packaging of viral genomes. However, understanding of RNA
dimerization has been hampered by the lack of systematic in vivo detection
methods. Here we show that CLASH, PARIS, and other RNA proximity ligation
methods detect RNA homodimers transcriptome-wide as "overlapping" chimeric
reads that contain more than one copy of the same sequence. Analysing
published proximity ligation datasets, we show that RNA:RNA homodimers
mediated by direct base-pairing are rare across the human transcriptome, but
highly enriched in specific transcripts, including U8 snoRNA, U2 snRNA and a
subset of tRNAs. Mutations in the homodimerization domain of U8 snoRNA
impede dimerization in vitro and disrupt zebrafish development in vivo,
suggesting an evolutionarily conserved role of this domain. Analysis of virusinfected cells reveals homodimerization of SARS-CoV-2 and Zika genomes,
mediated by specific palindromic sequences located within protein-coding
regions of N gene in SARS-CoV-2 and NS2A gene in Zika. We speculate that
regions of viral genomes involved in homodimerization may constitute effective
targets for antiviral therapies.