Related Experiment Video
Updated: Sep 30, 2025

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
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.
Abstract:
Deregulation of mRNA translation is a widespread characteristic of glioblastoma (GBM), aggressive malignant brain tumors that are resistant to conventional therapies. RNA-binding proteins (RBPs) play a critical role in translational regulation, yet the mechanisms and impact of these regulations on cancer development, progression and response to therapy remain to be fully understood. Here, we showed that hnRNP H/F RBPs are potent regulators of translation through several mechanisms that converge to modulate the expression and/or the activity of translation initiation factors. Among these, hnRNP H/F regulate the phosphorylation of eIF4E and its translational targets by controlling RNA splicing of the A-Raf kinase mRNA, which in turn modulates the MEK-ERK/MAPK signaling pathway. The underlying mechanism involves RNA G-quadruplex (RG4s), RNA structures whose modulation phenocopies hnRNP H/F translation regulation in GBM cells. Our results highlighted that hnRNP H/F are essential for key functional pathways regulating proliferation and survival of GBM, highlighting its targeting as a promising strategy for improving therapeutic outcomes.
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.
More Related Videos
Related Concept Videos
Regulation of Expression at Multiple Steps
Translational Regulation
Regulation of Angiogenesis and Blood Supply
Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Regulated mRNA Transport

