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Related Experiment Video

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Identification of Circular RNAs using RNA Sequencing
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Systematic loss-of-function screens identify pathway-specific functional circular RNAs.

Ling Liu1, Matthew Neve1, Laura Perlaza-Jimenez1,2

  • 1Department of Biochemistry and Molecular Biology, and Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

Nature Cell Biology
|August 2, 2024
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Summary

This study identifies functional circular RNAs (circRNAs) that regulate cellular pathways. Researchers screened thousands of human circRNAs to discover novel regulators of cancer cell proliferation and signaling pathways.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Circular RNAs (circRNAs) are a class of RNA molecules formed by back-splicing.
  • While some circRNAs have known functions, the pathways they regulate remain largely unexplored.
  • Understanding circRNA functions is crucial for deciphering complex cellular processes.

Purpose of the Study:

  • To identify functional circRNAs and the pathways they regulate.
  • To investigate the role of circRNAs in cancer cell proliferation and signaling.
  • To create a catalog of circRNAs with measurable functions.

Main Methods:

  • Generated a pooled short-hairpin RNA library targeting 3,354 human circRNAs.
  • Conducted loss-of-function proliferation screens in 18 cancer cell lines across four tissue types.
  • Validated findings using secondary screening and identified specific circRNA regulators.

Main Results:

  • Identified both context-specific and non-specific functional circRNAs.
  • Discovered circRNAs regulating their own precursors and those with independent functions.
  • Validated key circRNAs, including circRERE, circHUWE1, circSMAD2 (WNT pathway), and circMTO1 (MAPK signaling).

Conclusions:

  • This research provides insights into circRNA-mediated pathway regulation.
  • A catalog of functional circRNAs involved in cancer cell biology has been established.
  • The study highlights the diverse roles of circRNAs in cellular processes.