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

Authors :
Herviou P
Le Bras M
Dumas L
Hieblot C
Gilhodes J
Cioci G
Hugnot JP
Ameadan A
Guillonneau F
Dassi E
Cammas A
Millevoi S
Source :
Nature communications [Nat Commun] 2020 May 27; Vol. 11 (1), pp. 2661. Date of Electronic Publication: 2020 May 27.
Publication Year :
2020

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.

Details

Language :
English
ISSN :
2041-1723
Volume :
11
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
32461552
Full Text :
https://doi.org/10.1038/s41467-020-16168-x