Translational Regulation by hnRNP H/F Is Essential for the Proliferation and Survival of Glioblastoma

Morgane Le Bras1,2, Noah Gorelick3, Sylvain Pautet2

  • 1Cancer Research Centre of Toulouse, INSERM UMR 1037, 31037 Toulouse, France.

Cancers
|March 10, 2022
PubMed

Insights

RNA-binding proteins hnRNP H/F regulate glioblastoma (GBM) cell proliferation and survival by controlling mRNA translation. Targeting hnRNP H/F offers a promising strategy for improving GBM therapeutic outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor characterized by deregulated mRNA translation.
  • RNA-binding proteins (RBPs) are crucial in translational control, but their precise roles in GBM remain unclear.

Purpose of the Study:

  • To investigate the role of hnRNP H/F RNA-binding proteins in glioblastoma mRNA translation.
  • To elucidate the mechanisms by which hnRNP H/F influence GBM cell proliferation and survival.

Main Methods:

  • Analysis of hnRNP H/F regulation of translation initiation factors.
  • Investigation of hnRNP H/F control over A-Raf kinase mRNA splicing.
  • Assessment of RNA G-quadruplex (RG4) involvement in hnRNP H/F-mediated translation regulation.

Main Results:

  • hnRNP H/F proteins are potent regulators of mRNA translation in GBM cells.
  • hnRNP H/F control eIF4E phosphorylation and downstream signaling via A-Raf mRNA splicing.
  • Modulation of RNA G-quadruplex structures mimics hnRNP H/F effects on translation.

Conclusions:

  • hnRNP H/F proteins are essential for GBM proliferation and survival pathways.
  • Targeting hnRNP H/F represents a potential therapeutic strategy for glioblastoma.

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