Global mapping of RNA homodimers in living cells

Abstract

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.

Rights

http://creativecommons.org/licenses/by/4.0/

Cite as

Downloadable citations

Identifiers

DOI

https://doi.org/10.1101/gr.275900.121

Repository URI

https://www.research.ed.ac.uk/en/publications/2f6b036f-c6e9-4f40-a600-fc8b4a83f466