Ribosomal RNA 2′ O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

Marcel, Virginie; Kielbassa, Janice; Marchand, Virginie; Natchiar, K.S.; Paraqindes, Hermes; Long, Flora Nguyen Van; Ayadi, Lilia; Bourguignon‐Igel, Valérie; Monaco, Piero Lo; Monchiet, Déborah; Scott, Véronique; Tonon, Laurie; Bray, Susan E.; Diot, Alexandra; Jordan, Lee B.; Thompson, Alastair; Bourdon, Jean‐Christophe; Dubois, Thierry; André, Fabrice; Catez, Frédéric; Puisieux, Alain; Motorin, Yuri; Klaholz, Bruno P.; Viari, Alain; Diaz, Jean‐Jacques

doi:10.1093/narcan/zcab006

Cited by 6 publications

(14 citation statements)

References 1 publication

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“…Recently, a RiboMethSeq analysis was applied to large clinical cohorts of breast cancer tissues and diffuse large B-cell lymphoma samples [ 26 , 27 ]. Since identical analytical technique (albeit in different flavours) was applied in both studies, the results can be compared almost directly.…”

Section: Discussionmentioning

confidence: 99%

“…With the development of different versions of RiboMethSeq [ 8 , 24 , 25 ], see [ 23 ] for a review, a comprehensive profiling of variably modified rRNA Nm residues become possible, but was systematically performed only for some model human cell lines (e.g. HeLa/HCT116 cells) [ 5 ] as well as in two different cancer models: breast cancer tissues and B-cell lymphoma [ 26 , 27 ]. The latter study revealed pronounced hypomethylation of some rRNA Nm sites (namely 18S-Um354, 18S-Cm1440 and 28S-Gm4593).…”

Section: Introductionmentioning

confidence: 99%

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Constitutive and variable 2’-O-methylation (Nm) in human ribosomal RNA

et al. 2021

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Epitranscriptomic modifications of stable RNAs are dynamically regulated and specific profiles of 2ʹ-O-methylation in rRNA have been associated with distinct cancer types. However, these observations pointed out the existence of at least two distinct groups: a rather large group with constitutive rRNA Nm residues exhibiting a stable level of methylation and a more restricted set of variable modifications, giving rise to the concept of 'specialized ribosomes'. These heterogeneous ribosomes can modulate their translational properties and be key regulatory players, depending on the physiological state of the cell. However, these conclusions were drawn from a limited set of explored human cell lines or tissues, mostly related to cancer cells of the same type. Here, we report a comprehensive analysis of human rRNA Nm modification variability observed for >15 human cell lines grown in different media and conditions. Our data demonstrate that human Nm sites can be classified into four groups, depending on their observed variability. About ⅓ of rRNA 2ʹ-O-methylations are almost invariably modified at the same level in all tested samples (stable modifications), the second group of relatively invariant modifications (another ½ of the total) showing a slightly higher variance (low variable group) and two variable groups, showing an important heterogeneity. Mapping of these four classes on the human ribosome 3D structure shows that stably modified positions are preferentially located in the important ribosome functional sites, while variable and highly variable residues are mostly distributed to the ribosome periphery. Possible relationships of such stable and variable modifications to the ribosome functions are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Constitutive and variable 2’-O-methylation (Nm) in human ribosomal RNA

et al. 2021

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“…A first line of evidence supporting the hypothesis that tRNA and rRNA modifications are not static comes from the observation that these chemical decorations vary in human diseases including cancer [ 14–22 ]. For example, two recent studies revealed a global reduction of rRNA 2ʹ- O -methylation at some rRNA sites (named variable sites) in two types of human tumours compared to their corresponding level in normal tissue [ 21 , 22 ]. These new cancer-related hypomethylated patterns were found to be tumour-specific and associated with tumour aggressiveness [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, two recent studies revealed a global reduction of rRNA 2ʹ- O -methylation at some rRNA sites (named variable sites) in two types of human tumours compared to their corresponding level in normal tissue [ 21 , 22 ]. These new cancer-related hypomethylated patterns were found to be tumour-specific and associated with tumour aggressiveness [ 21 , 22 ]. In contrast, the global level of tRNA modifications is generally higher in cancer cells compared to their corresponding level in normal tissue [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the global level of tRNA modifications is generally higher in cancer cells compared to their corresponding level in normal tissue [ 23 ]. Based on these variations, both rRNA and tRNA modifications are now proposed as useful prognostic markers for cancer [ 14 , 21 , 22 , 24 , 25 ]. More generally, eukaryote tRNA modification levels have been shown to vary during cell cycle and in response to environmental stresses [ 5 , 26–31 ].…”

Section: Introductionmentioning

confidence: 99%

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Variations in transfer and ribosomal RNA epitranscriptomic status can adapt eukaryote translation to changing physiological and environmental conditions

2021

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The timely reprogramming of gene expression in response to internal and external cues is essential to eukaryote development and acclimation to changing environments. Chemically modifying molecular receptors and transducers of these signals is one way to efficiently induce proper physiological responses. Post-translation modifications, regulating protein biological activities, are central to many well-known signal-responding pathways. Recently, messenger RNA (mRNA) chemical (i.e. epitranscriptomic) modifications were also shown to play a key role in these processes. In contrast, transfer RNA (tRNA) and ribosomal RNA (rRNA) chemical modifications, although critical for optimal function of the translation apparatus, and much more diverse and quantitatively important compared to mRNA modifications, were until recently considered as mainly static chemical decorations. We present here recent observations that are challenging this view and supporting the hypothesis that tRNA and rRNA modifications dynamically respond to various cell and environmental conditions and contribute to adapt translation to these conditions.

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