INVESTIGATEUR ASSOCIE : STEFANIA MILLEVOI
RNA G-quadruplex structures
and adaptation to stress
G-quadruplex RNAs (RG4s) are non-canonical four-stranded structures known to play a role in the control of gene expression, from transcription to protein synthesis. Due to their potential impact on RNA biology, these structures could modulate cellular processes involved in cancer development and progression, opening attractive therapeutic opportunities (see our reviews: Millevoi, S. (2012) WiresRNA; Cammas, A. & Millevoi (2017) NAR; Dumas, L. (2021) TIBS).
Millevoi and A. Cammas contributed to the RG4 field by pointing out the existence of tunable conformations located within mRNAs encoding cancer proteins (VEGF, MST1R, TP53, USP1) (Decorsiere, A., (2011) Genes and Dev.; Cammas, A. (2015) RNA Biol.; Cammas, A. (2016) Oncotarget; Herviou, P., (2020) Nat. Comm). Our work contributed to demonstrate that the function of RG4s related to tumor progression and genomic instability is regulated by specific RNA binding proteins (RBPs) and RNA helicases and can be targeted by small molecules stabilizing RG4 conformations (Herviou, P. (2020) Nat. Comm).
Our general objective is to provide a comprehensive view at the transcriptomic/proteomic scale of i) the regulatory function fulfilled by RG4s in post-transcriptional regulation, ii) the RBPs associated to these structures, iii) the underlying regulatory mechanisms and signaling cascades targeting their activity. Ongoing work focuses on studying the RG4-mediated coordination of RNA programs ensuring metabolic adaptation in response to genotoxic stress.