Page 84 - ebook

[A. Biochemistry/Molecular Biology] A-42

Correlation of circRNA and THO/TREX complex for genome

integrity

Chulsung Park¹, Junho Hur¹*

¹Department of Biomedical Science, Graduate school of Biomedical Science & Engineering, Hanyang University,

Seoul 04763, Korea

Circular RNAs (circRNAs) are a class of highly conserved non-coding RNAs with circular forms in eukaryotic cells.

They are derived from exonic and intronic sequence by mRNA precursor back-splicing, have a covalent structure
that lacks both 5’ cap and 3’ poly(A) tail which protects from exoribonuclease. CircRNAs have several cellular

functions including miRNA sponging, protein sponging, 5’ cap-independent translation, and DNA; RNA hybrid
formation (R-loop). Recent studies suggested that circRNAs may be regulated by a conserved multi-subunit

THO/TREX complex, which is known to be required for the biogenesis of the export-competent mRNP. An RNAi
screen study in Drosophila cell line showed that a TREX component called Hel25E, an RNA-dependent ATPase and

RNA-DNA helicase, regulates the export of specific circRNAs from nuclear to cytoplasm. In this study, we sought to
ask if loss of THO complex subunit would increase the formation of R-loop which leads to genome instability. To

this end, we assessed whether depletion of THO/TREX complex disrupts circRNA export from nuclear to cytoplasm
and relate R-loop formation with circRNAs in the nucleus. We found that several circRNAs remained in the nuclei

of THO subunit K/O cells. The patterns of R-loops depletion by THO and circRNAs were overlapped.