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Co-existence of compulsory and plastic rRNA 2'-O-Methylation sites in human breast tumours

ABSTRACT: Emerging evidence suggests that changes in ribosomal RNA 2’O-ribose methylation (rRNA 2’OMe) in the human ribosome play a key role in regulating translation thereby contributing in setting particular phenotypes such as hallmarks of cancer cells. Here, by analysing the rRNA 2’OMe in a large series of 195 human primary breast tumours using the RiboMETH-seq approach we have identified the positions within the rRNA molecules which can tolerate the absence of 2’OMe in humans. The frequency of rRNA 2’OMe at some positions is highly stable between individuals (termed “stable”) whereas it can vary substantially at other positions (termed “variant”). Differential association of rRNA 2’OMe with breast cancer features, evolution and structure/function characteristics suggest the stable positions showing a low inter-variability might be required to maintain the core structure and thus the function of the ribosome – representing compulsory rRNA 2’OMe positions. In contrast, the variant positions displaying high inter-variability might be the source of regulatory events – representing plastic rRNA 2’OMe positions. Therefore our data issued from rRNA 2’OMe profiling of a large-scale human sample series bring the first compelling evidence to resolve two divergent long lasting visions of the role of rRNA 2’O-Me and sustain the emerging role of the ribosome plasticity in regulating translation in cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143415 | GEO | 2020/12/22

REPOSITORIES: GEO

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Stable nucleosome positions in HOX clusters; human K562 and HeLa cells

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2008-02-20 | GSE10042 | GEO

Alterations of ribosomal RNA pseudouridylation in human breast cancer

Project description:RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2’O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.

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2018-10-11 | GSE120450 | GEO

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Genome-wide mapping and functional analysis of DNA methylation in clonal invasive crayfish [WGBS]

2018-10-11 | GSE112409 | GEO

Site specific pseudouridine (Psi) on Leishmania rRNA regulates translation of subset of proteins

Project description:Leishmania are unicellular parasites that cycle between the insect and mammalian host and is the causative agent of Leishmaniasis. Previous studies from our lab suggested that individual rRNA modification such as pseudouridine (Psi) and 2-O-methylation are developmentally regulated during the complex life cycle of these parasites. Ablation of a single snoRNA guiding Psi in the inter-subunit bridge, helix69 of the ribosome affects its affinity to translate specific mRNA. Mutational analysis in the pseudouridylation pocket of this snoRNA supports the notion that the guided modification and not the chaperone activity, is essential for the observed phenotype. Structural studies using CryoEM suggested that a single Psi modification can affect the rRNA structure. We propose that alteration in rRNA modifications could generate ribosomes preferentially translating state-beneficial proteins.

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