circHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA

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.