PUBLICATION

Global mapping of RNA homodimers in living cells

Authors
Gabryelska, M.M., Badrock, A.P., Lau, J.Y., O'Keefe, R., Crow, Y.J., Kudla, G.
ID
ZDB-PUB-220326-14
Date
2022
Source
Genome research   32(5): 956-967 (Journal)
Registered Authors
Badrock, Andrew P.
Keywords
none
MeSH Terms
  • Animals
  • Base Sequence
  • COVID-19*
  • RNA, Small Nucleolar/genetics
  • RNA, Viral/genetics
  • SARS-CoV-2/genetics
  • Zebrafish/genetics
  • Zika Virus*/genetics
  • Zika Virus Infection*/genetics
PubMed
35332098 Full text @ Genome Res.
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. Analyzing 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 virus-infected 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping