The circRNA interactome-innovative hallmarks of the intra- and extracellular radiation response

• Published in: Oncotarget Vol. 8; no. 45; pp. 78397 - 78409
• Main Authors: O'Leary, Valerie Bríd, Smida, Jan, Matjanovski, Martina, Brockhaus, Corinna, Winkler, Klaudia, Moertl, Simone, Ovsepian, Saak Victor, Atkinson, Michael John
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 03-10-2017
• Subjects: Research Paper; WWOX; circRNA; KIRKOS; exosomes; QUAKING
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.19228

Generated by Quaking (QKI), circular RNAs (circRNAs) are newly recognised non-coding RNA (ncRNA) members characterised by tissue specificity, increased stability and enrichment within exosomes. Studies have shown that ionizing radiation (IR) can influence ncRNA transcription. However, it is unknown whether circRNAs or indeed QKI are regulated by IR. Microarray circRNA profiling and next generation sequencing revealed that circRNA expression was altered by low and medium dose exposure sourced predominantly from genes influencing the p53 pathway. CircRNAs
and
transcribed from the
(
) tumor suppressor (a p53 regulator) responded within hours to IR.
and
were present in exosomes yet exhibited differential transcript clearance between irradiated cell lines. Dual-quasar labelled probes and
hybridization demonstrated the intercellular distribution of
and
predominantly within the perinucleus. QKI knockdown removed nuclear expression of these circRNAs with no significant effect on cytosolic
and
Distinct QKI transcription between cell lines and its augmented interaction with
and
was noted post IR. This foremost study provides evidence that QKI and circRNAs partake in the cellular irradiation response.
and
as stable secreted circRNAs may afford vital characteristics worth syphoning as promising diagnostic radiotherapy biomarkers.