Methylation of Ribosomal RNA: A Mitochondrial Perspective

Sanchez, M Isabel G Lopez; Cipullo, Miriam; Gopalakrishna, Shreekara; Khawaja, Anas; Rorbach, Joanna

doi:10.3389/fgene.2020.00761

Cited by 25 publications

(30 citation statements)

References 137 publications

(202 reference statements)

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“…It is, however, possible that more modification sites will be identified in the future due to the recent advances in experimental tools, such as sequencing techniques and cryo-EM. The use of the latter, for instance, allowed us to visualize all five methylation sites in 12S rRNA [ 10 , 57 ].…”

Section: Mitoribosome Assembly Factorsmentioning

confidence: 99%

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Human Mitoribosome Biogenesis and Its Emerging Links to Disease

Sanchez

Krüger

Shiriaev

et al. 2021

IJMS

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Mammalian mitochondrial ribosomes (mitoribosomes) synthesize a small subset of proteins, which are essential components of the oxidative phosphorylation machinery. Therefore, their function is of fundamental importance to cellular metabolism. The assembly of mitoribosomes is a complex process that progresses through numerous maturation and protein-binding events coordinated by the actions of several assembly factors. Dysregulation of mitoribosome production is increasingly recognized as a contributor to metabolic and neurodegenerative diseases. In recent years, mutations in multiple components of the mitoribosome assembly machinery have been associated with a range of human pathologies, highlighting their importance to cell function and health. Here, we provide a review of our current understanding of mitoribosome biogenesis, highlighting the key factors involved in this process and the growing number of mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors that lead to human disease.

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Section: Mitoribosome Assembly Factorsmentioning

confidence: 99%

“…Methylation of mitoribosomal RNA is an emerging research field, and we are still at the beginning of understanding its biological significance. As this topic was covered in detail by a recent review [ 57 ], we will focus on the main aspects here.…”

Section: Mitoribosome Assembly Factorsmentioning

confidence: 99%

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

Sanchez

Krüger

Shiriaev

et al. 2021

IJMS

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“…Hence, homeostasis of the biogenesis and modification of mitochondrial ribosomes are essential for cellular metabolism and mitochondrial translation. Abnormal mitochondrial ribosome modification can lead to the interruption of mitochondrial protein synthesis and impedes assembly of the components of the mitochondrial respiratory chain, which usually leads to metabolic-related diseases ( 11 , 12 ). With the development of cryo-electron microscopy, nine modifications of mt-rRNA have been identified.…”

Section: Introductionmentioning

confidence: 99%

“…All corresponding modifying enzymes have been described to explore their effects on the biogenesis and function of mitochondria ( 9 , 10 , 12 , 13 ). The prominent modification of mammalian mt-rRNA involves catalysis by methyltransferases consisting of TRMT2B (modifies the nucleotide m 5 U429), METTL15 (modifies the nucleotide m 4 C839), NSUN4 (modifies the nucleotide m 5 C841), TFB1M (modifies the nucleotide

A936/7), TRMT61B (modifies the nucleotide m 1 A947), MRM1 (modifies the nucleotide Gm1145), MRM2/FTSJ2 (modifies the nucleotide Um1369), MRM3/RNMTL1 (modifies the nucleotide Gm1370) and RPUSD4 (modifies the nucleotide Ψ1397) ( 11 , 12 , 14 – 16 ). Deeper understanding of these regulators could aid the determination of the function and mechanism of mt-rRNA modification in post-transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

et al. 2021

Front. Immunol.

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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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“…Still, up to 2012 [ 8 ], only a single gene coding for the mammalian mitochondrial rRNA modification enzyme was known. Only recently, in 2019–2020 the list of mammalian mt-rRNA modification enzymes has been completed [ 9 , 10 , 11 , 12 , 13 ], allowing us to summarize the entire inventory of mammalian mt-RNA modification machinery ( Table 1 ), which is the subject of current review and several other excellent reviews on this topic [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Epitranscriptomics of Mammalian Mitochondrial Ribosomal RNA

Laptev

Dontsova

Сергиев

2020

Cells

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Modified nucleotides are present in all ribosomal RNA molecules. Mitochondrial ribosomes are unique to have a set of methylated residues that includes universally conserved ones, those that could be found either in bacterial or in archaeal/eukaryotic cytosolic ribosomes and those that are present exclusively in mitochondria. A single pseudouridine within the mt-rRNA is located in the peptidyltransferase center at a position similar to that in bacteria. After recent completion of the list of enzymes responsible for the modification of mammalian mitochondrial rRNA it became possible to summarize an evolutionary history, functional role of mt-rRNA modification enzymes and an interplay of the mt-rRNA modification and mitoribosome assembly process, which is a goal of this review.

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Methylation of Ribosomal RNA: A Mitochondrial Perspective

Cited by 25 publications

References 137 publications

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

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

Epitranscriptomics of Mammalian Mitochondrial Ribosomal RNA

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