The role of rRNA heterogeneity in cancer will be discussed. The story starts with our discovery that modifications of rRNA methylation occur during tumorigenesis (1,2). Modification of rRNA methylation pattern is associated with change in translational control of mRNAs encoding oncogenic proteins. We also revealed a novel facet of p53 protein, which can be considered as a player of translational regulation through an unexpected mechanism involving the ribosome (3,4).

We developed approaches to decipher the role of rRNA methylation in controlling translation during tumorigenesis and during treatment with anti-cancer molecules (5). Analyses of human samples series issued from different cancer types allowed identification of components involved in ribosome biogenesis and rRNA methylation as independent markers of poor prognosis (6-8). These components are involved either in the global or site-specific modulation of rRNA methylation pattern. Using bi-cistronic assays, in vitro translation and translatome analysis, we show that modulation of expression of rRNA methylation components associated with cancer patients’ outcome affect translational fidelity and translation initiation of subsets of mRNAs promoting tumorigenesis and escape to anti-cancer treatments (9).

1 - Belin S et al (2009) PLoS ONE 4, e7147

2 - Marcel V et al. (2013) Cancer Cell 24, 318–330

3 - Marcel V et al (2015) Oncogene 34, 5513-23

4 – Sharma S (2017) Sci Rep 7, 11490

5 – Bash-Imam Z (2017) Oncotarget 8, 46219-46233

6 – Nguyen Van Long et al. (2018) Cancers 10, 390

7 – Gachet et al. (2018) Cancer Discovery pii : CD-17-0831

8 – Marcel et al. (2020) NAR Cancer, 2, N°4, 1. doi : 10.1093/narcan/zcaa036

9 - Erales J et al (2017) PNAS 114, 12934-12939

Contact : karin.sadoul@univ-grenoble-alpes.fr