Genetic and epigenetic defects of the RNA modification machinery in cancer

Trends in Genetics, Journal Year: 2022, Volume and Issue: 39(1), P. 74 - 88

Published: Nov. 12, 2022

Cancer was initially considered to be an exclusively genetic disease, but interplay of dysregulated and epigenetic mechanisms is now known contribute the cancer phenotype. More recently, chemical modifications RNA molecules - so-called epitranscriptome have been found regulate various aspects function homeostasis. Specific enzymes, as RNA-modifying proteins (RMPs), are responsible for depositing, removing, reading in RNA. Intensive investigations epitranscriptomic field recent years, conjunction with great technological advances, revealed critical role regulating numerous cellular pathways. Furthermore, growing evidence has that modification machinery often altered human cancers, highlighting enormous potential RMPs pharmacological targets or diagnostic markers.

Language: Английский

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Navigating the pitfalls of mapping DNA and RNA modifications

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(6), P. 363 - 381

Published: Jan. 18, 2023

Language: Английский

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N1-methylation of adenosine (m1A) in ND5 mRNA leads to complex I dysfunction in Alzheimer’s disease

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1427 - 1439

Published: Jan. 29, 2024

Abstract One mechanism of particular interest to regulate mRNA fate post-transcriptionally is modification. Especially the extent m 1 A methylation highly discussed due methodological differences. However, one single site in mitochondrial ND5 was unanimously reported by different groups. a subunit complex I respiratory chain. It considered essential for coupling oxidation and proton transport. Here we demonstrate that this might be involved pathophysiology Alzheimer’s disease (AD). pathological hallmarks neurodegenerative dysfunction, mainly induced Amyloid β (Aβ). Aβ disturbs functions IV molecular dysfunction still not fully understood. We found enhanced an AD cell model as well patients. Formation catalyzed increased TRMT10C protein levels, leading translation repression ND5. As consequence, here demonstrated first time, leads dysfunction. Our findings suggest newly identified Aβ-induced

Language: Английский

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Epitranscriptome: Review of Top 25 Most-Studied RNA Modifications

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13851 - 13851

Published: Nov. 10, 2022

The alphabet of building blocks for RNA molecules is much larger than the standard four nucleotides. diversity achieved by post-transcriptional biochemical modification these nucleotides into distinct chemical entities that are structurally and functionally different from their unmodified counterparts. Some modifications constituent critical functions, while others serve as dynamic markings to regulate fate specific molecules. Together, form epitranscriptome, an essential layer cellular biochemistry. As time writing this review, more 300 all three life domains have been identified. However, only a few most well-established included in reviews on topic. To provide complete overview current state research we analyzed extent available information known modifications. We selected 25 describe detail. Summarizing our findings, status identify further developments field.

Language: Английский

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Emerging Roles of RNA Methylation in Development

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3417 - 3427

Published: Nov. 15, 2023

More than 170 different types of chemical modifications have been identified on diverse RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) ubiquitous post-transcriptional modification are widely involved in regulating metabolic processes such RNA degradation, translation, stability, export, mediating important physiological pathological stress regulation, immune response, development, tumorigenesis. Recently, regulatory role during developmental is getting more attention. Therefore, development low-input even single-cell high-resolution sequencing technologies crucial for exploration roles these biological events trace samples.This account focuses various processes. We describe distribution characteristics modifications, catalytic enzymes, binding proteins, technologies. dynamically reversible, which can be catalyzed by methyltransferases eliminated demethylases. m6A most abundant eukaryote mRNA, mainly concentrated near stop codon, involves metabolism regulation. m5C, another studied modification, has a organisms species, enriched regions downstream translation initiation sites broadly distributes across whole coding sequence (CDS) mammalian mRNAs. m1A, with lower abundance m6A, distributed types, locates 5' untranslated region (5'UTR) mRNA regulates translation. m7G, one common eukaryotes, at cap internal positions RNAs recently gained considerable attention.Thanks to technology, found regulate tumorigenic process, including tumor proliferation, invasion, metastasis modulating oncogenes suppressor genes, affect oocyte maturation embryonic through maternal zygotic genes. m5C related proteins participate plant growth, neural stem cell differentiation dependent manner. m1A also revealed m7G dysregulation neurodevelopmental disorders neurodegenerative diseases.Collectively, we summarized gradually exhibited methylation discussed possibility candidate biomarkers potential therapeutic targets. The technological anticipated major driving force expand our knowledge this field.

Language: Английский

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MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 7, 2023

Internal modifications of mRNA have emerged as widespread and versatile regulatory mechanism to control gene expression at the post-transcriptional level. Most these are methyl groups, making S-adenosyl-L-methionine (SAM) a central metabolic hub. Here we show that labeling with clickable precursor SAM, propargyl-selenohomocysteine (PSH), enables detection identification various methylation sites. Propargylated A, C, G nucleosides form detectable amounts via intracellular generation corresponding SAM analogue. Integration into next sequencing mapping N6-methyladenosine (m6A) 5-methylcytidine (m5C) sites in single nucleotide precision (MePMe-seq). Analysis termination profiles can be used distinguish m6A from 2'-O-methyladenosine (Am) N1-methyladenosine (m1A) MePMe-seq overcomes problems antibodies for enrichment sequence-motifs evaluation, which was limiting previous methodologies. Metabolic facilitates joint evaluation RNA potentially DNA proteins.

Language: Английский

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Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.

Language: Английский

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RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate multifactorial. Recently, post-transcriptional modifications (PTMs) RNA, with particular focus on mRNA methylation, have been gaining increasing attention. At present, several regulatory genes associated methylation identified closely neurodegenerative disorders. This review aimed summarize RNA enzymes system, including writer, reader, eraser proteins delve into their functions in central nervous system (CNS), hoping open new avenues for exploring mechanisms therapeutic strategies NDs. studies highlighted critical role development function CNS, abnormalities this process may contribute brain damage NDs, aberrant expression involved has implicated onset

Language: Английский

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Role of transcription factors, noncoding RNAs, epitranscriptomics, and epigenetics in post‐ischemic neuroinflammation

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 26, 2024

Abstract Post‐stroke neuroinflammation is pivotal in brain repair, yet persistent inflammation can aggravate ischemic damage and hamper recovery. Following stroke, specific molecules released from cells attract activate central peripheral immune cells. These subsequently release diverse inflammatory within the brain, initiating a sequence of events, including activation transcription factors different cell types that modulate gene expression influence outcomes; interactive action various noncoding RNAs (ncRNAs) to regulate multiple biological processes inflammation, epitranscriptomic RNA modification controls processing, stability, translation; epigenetic changes DNA methylation, hydroxymethylation, histone modifications crucial managing genic response stroke. Interactions among these events further affect post‐stroke shape depth functional outcomes. We highlighted aspects this review postulate deciphering mechanisms for identifying therapeutic targets alleviate dysfunction enhance

Language: Английский

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M6AREG: m6A-centered regulation of disease development and drug response

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D1333 - D1344

Published: Sept. 6, 2022

Abstract As the most prevalent internal modification in eukaryotic RNAs, N6-methyladenosine (m6A) has been discovered to play an essential role cellular proliferation, metabolic homeostasis, embryonic development, etc. With rapid accumulation of research interest m6A, its crucial roles regulations disease development and drug response are gaining more attention. Thus, a database offering such valuable data on m6A-centered regulation is greatly needed; however, no as yet available. Herein, new named ‘M6AREG’ developed (i) systematically cover, for first time, effects both response, (ii) explicitly describe molecular mechanism underlying each type (iii) fully reference collected by cross-linking existing databases. Since accumulated researchers diverse disciplines (such pathology pathophysiology, clinical laboratory diagnostics, medicinal biochemistry design), M6AREG expected have many implications future conduct m6A-based studies. It currently accessible all users at: https://idrblab.org/m6areg/

Language: Английский

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