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| Status |
Public on May 02, 2023 |
| Title |
Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability [ncRNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
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| Overall design |
Guthrie cards/neonatal blood spots from 8 control individuals (with no known blood, or other cancer) and 8 individuals who developed infant leukemia under the age of 10 associated with rearrangements in the MLL gene.
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| |
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| Contributor(s) |
Marri S, Conn SJ |
| Citation(s) |
37295428 |
| |
| Submission date |
Nov 02, 2022 |
| Last update date |
Aug 01, 2023 |
| Contact name |
Simon Conn |
| E-mail(s) |
simon.conn@flinders.edu.au
|
| Organization name |
Flinders University
|
| Department |
College of Medicine and Public Health
|
| Lab |
Circular RNAs in Cancer Laboratory
|
| Street address |
Sturt Road, Bedford Park
|
| City |
Adelaide |
| State/province |
South Australia |
| ZIP/Postal code |
5042 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE125986 |
Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability |
|
| Relations |
| BioProject |
PRJNA896982 |
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