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IGF2BP3 promotes mRNA degradation through internal m7G modification

Chang Liu1,2,3, Xiaoyang Dou1,2, Yutao Zhao1,2

  • 1Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, 60637, USA.

Nature Communications
|August 28, 2024
PubMed

Insights

IGF2BP proteins bind internal mRNA m7G modifications, impacting cancer cell metabolism and progression. IGF2BP3 promotes degradation of m7G targets, influencing glioblastoma chemosensitivity and progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Internal mRNA m7G modification and METTL1 are linked to cell metabolism and cancer.
  • IGF2BP family proteins are implicated in RNA regulation.

Purpose of the Study:

  • To investigate the interaction of IGF2BP proteins with internal mRNA m7G.
  • To determine the role of IGF2BP3 in cancer cell metabolism and glioblastoma progression.

Main Methods:

  • RNA immunoprecipitation assays to detect IGF2BP binding to m7G modified RNA.
  • Analysis of mRNA degradation rates and protein levels.
  • CRISPR-Cas13b system for site-specific targeting of m7G modifications.

Main Results:

  • IGF2BP1-3 proteins preferentially bind internal mRNA m7G.
  • IGF2BP3 promotes degradation of m7G target transcripts, including TP53, in cancer cells.
  • Modulating IGF2BP3 or m7G levels affects glioblastoma progression and chemosensitivity.

Conclusions:

  • IGF2BP proteins, particularly IGF2BP3, play a significant role in regulating m7G modified transcripts in cancer.
  • Targeting m7G modification or IGF2BP3 offers potential therapeutic strategies for glioblastoma.

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