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Updated: Jul 19, 2025

Identification of Circular RNAs using RNA Sequencing
08:25

Identification of Circular RNAs using RNA Sequencing

Published on: November 14, 2019

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The dark side of circular RNA, a new driver of genome instability

Ajit Kumar Sharma1, Anish Thomas1

  • 1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Cell Chemical Biology
|August 18, 2023
PubMed

Insights

Circular RNAs (circRNAs) can form DNA hybrids, driving genetic rearrangements in MLL/KMT2A. This discovery sheds light on aggressive acute leukemias and novel therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Circular RNAs (circRNAs) are a class of RNA molecules with a unique covalently closed structure.
  • The biological functions of circRNAs remain largely unexplored.
  • Specific genetic rearrangements involving MLL/KMT2A are hallmarks of aggressive acute leukemias.

Purpose of the Study:

  • To investigate the functional role of circRNAs in cancer.
  • To explore the interaction between circRNAs and DNA.
  • To elucidate the mechanism driving MLL/KMT2A genetic rearrangements in acute leukemia.

Main Methods:

  • Analysis of circRNA-DNA interactions.
  • Investigation of circRNA binding to cognate DNA loci.
  • Assessment of circRNA-mediated genetic rearrangements in MLL/KMT2A.

Main Results:

  • Demonstrated that circRNAs can bind to specific DNA sequences, forming circRNA-DNA hybrids termed 'circR loops'.
  • Showcased that these circR loops are responsible for inducing genetic rearrangements at the MLL/KMT2A gene loci.
  • Established a direct link between circRNA activity and the development of aggressive acute leukemias.

Conclusions:

  • Circular RNAs play a direct role in driving oncogenic genetic rearrangements.
  • The formation of circRNA-DNA hybrids (circR loops) is a novel mechanism contributing to MLL/KMT2A-driven leukemogenesis.
  • These findings open new avenues for understanding and potentially targeting aggressive acute leukemias.

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