Profiling of ribose methylations in ribosomal RNA from diffuse large B-cell lymphoma patients for evaluation of ribosomes as drug targets

Krogh, Nicolai; Asmar, Fazila; Côme, Christophe; Munch-Petersen, Helga Fibiger; Grønbæk, Kirsten; Nielsen, Henrik

doi:10.1093/narcan/zcaa035

Cited by 31 publications

(44 citation statements)

References 55 publications

(80 reference statements)

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“…Based on this latter hypothesis, variations in rRNA 2 Ome can be interpreted as a biological noise. However, the observed increase in the rRNA 2 Ome level in some DLCBL and AML1-ETO-driven AML patients, and the correlation between SNORD expression and rRNA 2 Ome levels suggests that the variation of rRNA 2 Ome, at least at some sites, is cancer-specific or even tumor-specific [32,52,70]. In addition to being specific in regard to the nature of the tumor, rRNA 2 Ome levels are also different at some particular sites when comparing three distinct normal human organs (i.e., brain, liver, and skeletal muscle), supporting the tissue-specificity of rRNA 2 Ome [70].…”

Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

“…First, the decrease in SNORD expression may be responsible for the decreased rRNA 2 Ome levels, especially for the three sites with the most important variation, as observed in AML1-ETOdependent AML [55]. Second, the global decrease in rRNA 2 Ome could be caused by a passive effect driven by the hyperproliferation of cells, as the significant decrease in 2 Ome correlates with an increase in the proliferative Ki67 labelling index [70]. Indeed, rRNA synthesis is hyperactivated in cancer cells to maintain a high level of protein synthesis, essential for sustaining an hyperproliferative rate [72].…”

Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

“…In late 2020, the first evaluation of the complete diversity of rRNA 2 Ome in human cancer samples was established using the RiboMeth-seq technology by two labs in backto-back publications [70,71]. As in previous RTL-P analyses performed on blood samples, one study established the rRNA 2 Ome profile of 17 diffuse large B-cell lymphoma (DL-BCL) patient samples and three healthy donors using an IonTorrent-based RiboMeth-seq approach [70]. In this cohort, the difference between rRNA 2 Ome levels of each individual DLBCL samples and the mean of rRNA 2 Ome levels of normal samples was estimated for 110 rRNA 2 Ome sites.…”

Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

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2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases

Jaafar

Paraqindes

Gabut

et al. 2021

Cells

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Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2′O-ribose methylation (2′Ome), intrinsically occur in many organisms. In the last 5 years, accumulating reports have illustrated that rRNA 2′Ome varies in human cell lines but also in living organisms (yeast, plant, zebrafish, mouse, human) during development and diseases. These rRNA 2′Ome variations occur either within a single cell line, organ, or patient’s sample (i.e., intra-variability) or between at least two biological conditions (i.e., inter-variability). Thus, the ribosomes can tolerate the absence of 2′Ome at some specific positions. These observations question whether variations in rRNA 2′Ome could provide ribosomes with particular translational regulatory activities and functional specializations. Here, we compile recent studies supporting the heterogeneity of ribosome composition at rRNA 2′Ome level and provide an overview of the natural diversity in rRNA 2′Ome that has been reported up to now throughout the kingdom of life. Moreover, we discuss the little evidence that suggests that variations of rRNA 2′Ome can effectively impact the ribosome activity and contribute to the etiology of some human diseases.

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Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

Section: Diversity Of Rrna 2 Ome Profiles In Human Cancer Tissuesmentioning

confidence: 99%

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2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases

Jaafar

Paraqindes

Gabut

et al. 2021

Cells

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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][15][16][17][18][19][20][21][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 cancerrelated hypomethylated patterns were found to be tumourspecific and associated with tumour aggressiveness [21,22].…”

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][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

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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Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B‐cell lymphoma

Huang

Xie

et al. 2022

Cancer Medicine

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Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

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Profiling of ribose methylations in ribosomal RNA from diffuse large B-cell lymphoma patients for evaluation of ribosomes as drug targets

Cited by 31 publications

References 55 publications

2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases

2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases

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

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B‐cell lymphoma

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