hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma.

Abstract

RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation. Our results identified hnRNP H/F as important components of the cytoplasmic machinery modulating the structural integrity of RG4s, revealed their function in RG4-mediated translation and uncovered the underlying molecular mechanism impacting the cellular stress response linked to the outcome of glioblastoma.

• Authors: Pauline Herviou, Morgane Le Bras, Leïla Dumas, Corinne Hieblot, Julia Gilhodes, Gianluca Cioci, Jean-Philippe Hugnot, Alfred Ameadan, François Guillonneau, Erik Dassi, Anne Cammas, Stefania Millevoi
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 2661 (05 27 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32461552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heterogeneous-Nuclear Ribonucleoprotein Group F-H
• RNA, Messenger
• DHX36 protein, human
• DEAD-box RNA Helicases

Topics

• Brain Neoplasms (physiopathology)
• Cell Line, Tumor
• DEAD-box RNA Helicases (metabolism)
• G-Quadruplexes
• Gene Expression Regulation (physiology)
• Genomic Instability (physiology)
• Glioblastoma (physiopathology)
• Heterogeneous-Nuclear Ribonucleoprotein Group F-H (metabolism)
• Humans
• RNA, Messenger (metabolism)