Loss of m1acp3Ψ ribosomal RNA modification is a major feature of cancer

Maturation of pre-ribosomal RNA (pre-rRNA) in eukaryotic cells takes place in the nucleolus and involves a large number of cleavage events, which frequently follow alternative pathways. In addition, rRNAs are extensively modified, with the methylation of the 2'-hydroxyl group of sugar residues and conversion of uridines to pseudouridines being the most frequent modifications. Both cleavage and modification reactions of pre-rRNAs are assisted by a variety of small nucleolar RNAs (snoRNAs), which function in the form of ribonucleoprotein particles (snoRNPs). The majority of snoRNAs acts as guides directing site-specific 2'-O-ribose methylation or pseudouridine formation. Over one hundred RNAs of this type have been identified to date in vertebrates and the yeast Saccharomyces cerevisiae. This number is readily explained by the findings that one snoRNA acts as a guide usually for one or at most two modifications, and human rRNAs contain 91 pseudouridines and 106 2'-O-methyl residues. In this article we review information about the biogenesis, structure and function of guide snoRNAs.

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Health Through Ribosomal RNA Modification

Science ◽

10.1126/science.299.5604.161l ◽

2003 ◽

Vol 299 (5604) ◽

pp. 161l-161

Keyword(s):

Ribosomal Rna ◽

Rna Modification

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nanoDoc: RNA modification detection using Nanopore raw reads with Deep One-Class Classification

10.1101/2020.09.13.295089 ◽

2020 ◽

Author(s):

Hiroki Ueda

Keyword(s):

Neural Network ◽

Single Molecule ◽

Ribosomal Rna ◽

High Throughput Sequencing ◽

Area Under The Curve ◽

Rna Modification ◽

Current Signal ◽

Experimental Approaches ◽

One Class Classification

AbstractAdvances in Nanopore single-molecule direct RNA sequencing (DRS) have presented the possibility of detecting comprehensive post-transcriptional modifications (PTMs) as an alternative to experimental approaches combined with high-throughput sequencing. It has been shown that the DRS method can detect the change in the raw electric current signal of a PTM; however, the accuracy and reliability still require improvement.Here, we presented a new software, called nanoDoc, for detecting PTMs from DRS data using a deep neural network. Current signal deviations caused by PTMs are analyzed via Deep One-Class Classification with a convolutional neural network. Using a ribosomal RNA dataset, the software archive displayed an area under the curve (AUC) accuracy of 0.96 for the detection of 23 different kinds of modifications in Escherichia coli and Saccharomyces cerevisiae. We also demonstrated a tentative classification of PTMs using unsupervised clustering. Finally, we applied this software to severe acute respiratory syndrome coronavirus 2 data and identified commonly modified sites among three groups. nanoDoc is open source (GPLv3) and available at https://github.com/uedaLabR/nanoDoc

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Loss of m1acp3Ψ ribosomal RNA modification is a major feature of cancer

10.1101/840132 ◽

2019 ◽

Author(s):

Artem Babaian ◽

Katharina Rothe ◽

Dylan Girodat ◽

Igor Minia ◽

Sara Djondovic ◽

...

Keyword(s):

Ribosomal Rna ◽

Ribosomal Proteins ◽

18S Rrna ◽

Rna Modification ◽

Nucleotide Variation ◽

Catalytic Core ◽

Single Nucleotide ◽

Domains Of Life ◽

Cancer Types ◽

Knockout Model

SummaryThe ribosome is an RNA-protein complex essential for translation in all domains of life. The structural and catalytic core of the ribosome is its ribosomal RNA (rRNA). While mutations in ribosomal protein (RP) genes are known drivers of oncogenesis, oncogenic rRNA variants have remained elusive. We discovered a cancer-specific single nucleotide variation in 18S rRNA at nucleotide 1248.U in up to 45.9% of colorectal carcinoma (CRC) patients and present across >22 cancer types. This is the site of a unique hyper-modified base, 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (m1acp3Ψ), a >1 billion years conserved RNA modification at the ribosome’s peptidyl decoding-site. A sub-set of CRC tumors we term ‘hypo-m1acp3Ψ’, show sub-stoichiometric m1acp3Ψ-modification unlike normal control tissues. A m1acp3Ψ knockout model and hypo-m1acp3Ψ patient tumors share a translational signature, characterized by highly abundant ribosomal proteins. Thus, m1acp3Ψ-deficient rRNA forms an uncharacterized class of ‘onco-ribosome’ which may serve as a chemotherapeutic target for treating cancer patients.

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Human Mitochondrial Ribosomal RNA Modification-Based Classification Contributes to Discriminate the Prognosis and Immunotherapy Response of Glioma Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.722479 ◽

2021 ◽

Vol 12 ◽

Author(s):

Peng Wang ◽

Jingying Li ◽

Miaojing Wu ◽

Minghua Ye ◽

Kai Huang ◽

...

Keyword(s):

Ribosomal Rna ◽

Progression Free Survival ◽

Rna Modification ◽

Clinicopathologic Characteristics ◽

Free Survival ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Number Variation ◽

Cell Death Protein ◽

Immune Checkpoint Blockers

BackgroundEpigenetic regulations of the tumor microenvironment (TME) and immunotherapy have been investigated in recent years. Nevertheless, the potential value of mitochondrial ribosomal RNA (mt-rRNA) modification in regulation of the TME and immunotherapy remains unknown.MethodsWe comprehensively investigated the mt-rRNA-modification patterns in glioma patients based on nine regulators of mt-rRNA. Subsequently, these modification patterns were correlated systematically with immunologic characteristics and immunotherapy. An “mt-rRNA predictor” was constructed and validated in multiple publicly available cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.ResultsTwo distinct patterns of mt-rRNA modification were determined based on the evidence that nine regulators of mt-rRNA correlated significantly with most clinicopathologic characteristics, immunomodulators, TME, immune-checkpoint blockers (ICBs), and prognosis. Patients with mt-rRNA subtype II presented significantly poorer overall survival/progression-free survival (OS/PFS), but higher tumor mutational burden (TMB), more somatic mutations, and copy number variation (CNV). These two mt-rRNA subtypes had distinct TME patterns and responses to ICB therapy. An mt-rRNA predictor was constructed and validated in four glioma cohorts. The subtype with high mt-rRNA score, characterized by increased TMB, infiltration of immune cells, and activation of immunity, suggested an immune-activated phenotype, and was also linked to greater sensitivity to immunotherapy using anti-programmed cell death protein 1 (PD-1) but resistance to temozolomide.ConclusionsRegulators of mt-rRNA modification have indispensable roles in the complexity and diversity of the TME and prognosis. This novel classification based on patterns of mt-rRNA modification could provide an effective prognostic predictor and guide more appropriate immunotherapy/chemotherapy strategies for glioma patients.

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