RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

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Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 41(3), P. 344 - 354

Published: Oct. 27, 2022

Abstract Functional characterization of pseudouridine (Ψ) in mammalian mRNA has been hampered by the lack a quantitative method that maps Ψ whole transcriptome. We report bisulfite-induced deletion sequencing (BID-seq), which uses bisulfite-mediated reaction to convert stoichiometrically into upon reverse transcription without cytosine deamination. BID-seq enables detection abundant sites with stoichiometry information several human cell lines and 12 different mouse tissues using 10–20 ng input RNA. uncover consensus sequences for assign ‘writer’ proteins individual deposition. Our results reveal transcript stabilization role installed TRUB1 cancer cells. also detect presence within stop codons confirm promoting codon readthrough vivo. will enable future investigations roles diverse biological processes.

Language: Английский

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RNA modifications in physiology and disease: towards clinical applications

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 104 - 122

Published: Sept. 15, 2023

Language: Английский

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tRNA modification dynamics from individual organisms to metaepitranscriptomics of microbiomes

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(5), P. 891 - 906

Published: Jan. 14, 2022

Language: Английский

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N1-methyladenosine modification in cancer biology: Current status and future perspectives

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 6578 - 6585

Published: Jan. 1, 2022

Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N1-methyladenosine (m1A), which is dynamically regulated by writers, erasers readers, has been found as a reversible modification tRNA, mRNA, rRNA long non-coding RNA (lncRNA). m1A impacts on the processing, structure functions of targets. Increasing studies reveal critical roles its regulators tumorigenesis. Due to positive relevance between cancer development, targeting m1A-related attention. In this review, we summarized current understanding RNAs, covering modulation biology, well possibility potential target for diagnosis therapy.

Language: Английский

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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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RNA modification: mechanisms and therapeutic targets

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 24, 2023

Abstract RNA modifications are dynamic and reversible chemical on substrate that regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes various diseases, such as development cancer other diseases. With help advanced sequencing technologies, role has caught increasing attention human diseases scientific research. In this review, we briefly summarized basic mechanisms several common modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing ac4C. Importantly, discussed their potential functions cancer, neurological disorders, cardiovascular metabolic genetic developmental well immune disorders. Through “writing-erasing-reading” mechanisms, regulate stability, translation, localization pivotal disease-related mRNAs to manipulate disease development. Moreover, also highlighted review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most which designed against m6A-related enzymes, METTL3, FTO ALKBH5. This provides clues for clinical therapy future study directions modification field. More in-depth studies further activators needed a thorough understanding epitranscriptomics diagnosis, treatment, prognosis

Language: Английский

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RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 27, 2024

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding pathophysiology, inspiring development therapeutics. As a crucial component epigenetics at post-transcription level, RNA modification significantly determines fates, further affecting various biological processes cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells different stages immunological contexts. In this review, we characterize distribution features, modifying mechanisms functions 8 modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively most studied types. Then regulatory roles these diverse health disease contexts comprehensively described, categorized as glucose, lipid, amino acid, mitochondrial metabolism. And highlight regulation modifications immunometabolism, influencing responses. Above all, provide thorough discussion about clinical implications metabolism-targeted therapy immunotherapy, progression modification-targeted agents, its potential RNA-targeted Eventually, give legitimate perspectives for future researches field from methodological requirements, mechanistic insights, to therapeutic applications.

Language: Английский

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m1A RNA Modification in Gene Expression Regulation

Genes, Journal Year: 2022, Volume and Issue: 13(5), P. 910 - 910

Published: May 19, 2022

N1-methyladenosine (m1A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA mRNA. Recent studies based on technical advances in analytical chemistry high-throughput sequencing methods have revealed the crucial roles of m1A gene regulation biological processes. In this review, we focus progress study methyltransferases, demethylases m1A-dependent RNA-binding proteins highlight mechanisms functions modification, as well its association with human disease. We also summarize current understanding detection approaches for modification.

Language: Английский

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METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106840 - 106840

Published: June 26, 2023

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of fission is not well appreciated cardiac fibrosis, which accompanied enhanced fibroblast We investigated causes consequences fibrosis using cultured cells, animal models, clinical samples. Increased METTL3 expression caused excessive fission, resulting migration fibroblasts that lead to fibrosis. Knockdown suppressed inhibiting for ameliorating Elevated N6-methyladenosine (m6A) levels were associated with low long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation GAS5 induced its degradation, dependent YTHDF2. could interact marker Drp1 directly; overexpression Drp1-mediated produced opposite effect. Clinically, increased YTHDF2 corresponded decreased expression, mRNA content human heart tissue atrial fibrillation. describe a novel mechanism wherein boosts proliferation, migration: catalyzes YTHDF2-dependent manner. Our findings provide insight into development preventative measures

Language: Английский

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