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Related Experiment Video

Updated: Jun 20, 2025

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circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.

Trine Line Hauge Okholm1,2,3, Andreas Bjerregaard Kamstrup4, Morten Muhlig Nielsen1,3

  • 1Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.

Elife
|July 23, 2024
PubMed
Summary

Circular RNA circHIPK3 regulates gene expression by sequestering IGF2BP2, influencing cell proliferation. This ceRNA mechanism involves circHIPK3 nucleating IGF2BP2 condensates, impacting STAT3 mRNA levels.

Keywords:
RNA-binding proteinsbladder cancercell biologycircular RNAcomputational biologyhumansystems biology

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Area of Science:

  • Molecular Biology
  • Genomics
  • RNA Biology

Background:

  • Circular RNAs (circRNAs) are key regulators of gene expression with roles in disease pathogenesis.
  • circHIPK3 is a novel circRNA implicated in cellular regulation.

Purpose of the Study:

  • To elucidate the gene-regulatory role of circHIPK3.
  • To investigate the mechanism by which circHIPK3 influences gene expression and cell proliferation.

Main Methods:

  • Analysis of large genomics datasets and RNA sequencing.
  • Time-course depletion of circHIPK3 and RNA-binding proteins.
  • Expression-coupled motif analysis, eCLIP, and RNA immunoprecipitation assays.
  • Absolute copy number quantification and investigation of phase separation.

Main Results:

  • circHIPK3 harbors an 11-mer motif that binds IGF2BP2, acting as a competing endogenous RNA (ceRNA).
  • circHIPK3 regulates STAT3 mRNA levels by modulating IGF2BP2 binding.
  • circHIPK3 can induce IGF2BP2 condensation, potentially via phase separation, independent of a 1:1 ceRNA stoichiometry.

Conclusions:

  • circHIPK3 regulates gene expression and cell proliferation through IGF2BP2 condensation.
  • This mechanism highlights a novel mode of circRNA-mediated gene regulation impacting key cellular factors.