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Diversity in rRNA 2’Ome profiles in cancer and impact on translational regulation

Conference of Virginie Marcel, Cancer Research Center of Lyon, UMR INSERM 1052 CNRS 5286, Centre Léon Bérard, Université Lyon 1, Nuclear domains and pathologies team, Lyon, France

Videoconference given on Tuesday 10 May 2022 as part of the CRCT’s “RNA and Cancer” axis 2 seminar

While the ribosome was considered for over 40 years as a neutral actor of gene expression, it now appears as a key regulator of translation through modulation of its composition, including via chemical modifications of ribosomal RNAs (rRNAs). In cellular models, we revealed that ribose 2’-Omethylation (2’Ome) of rRNA can be modulated in human and become a source of ribosome diversity. We reported that 2’Ome is altered during tumorigenesis and directly affects translational behavior of ribosomes toward mRNA subsets. However, whether alteration of rRNA 2’Ome occurs in “real-life” remained to be demonstrated. Thanks to an innovative omic technology, the RiboMETH-seq, we made the first demonstration that rRNA 2’Ome is altered in different cancer types, including breast cancer and glioma. It appears that variability in rRNA 2’Ome level is restricted to only a subset of positions. Moreover, comparison of several adult tumors indicates that most of these variable sites are common to different tumor sites while few of them are specific to particular cancer type. Our data support the recent entry of the ribosome into the emerging field of epitranscriptomics.

References

(1) Marcel et al. (2013) Cancer Cell 24, 318-330.

(2) Erales et al. (2017) PNAS 114, 12934-12939.

(3) Marcel et al. (2020) NAR Cancer 2, 318.

(4) Jaafar et al. (2021) Cells 10, 1948.

Videoconference