Cell, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)
Опубликована: Сен. 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.
Язык: Английский
Процитировано
210
Nature Biotechnology, Год журнала: 2022, Номер 41(3), С. 344 - 354
Опубликована: Окт. 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.
Язык: Английский
Процитировано
163
Nature Reviews Genetics, Год журнала: 2023, Номер 25(2), С. 104 - 122
Опубликована: Сен. 15, 2023
Язык: Английский
Процитировано
139
Molecular Cell, Год журнала: 2022, Номер 82(5), С. 891 - 906
Опубликована: Янв. 14, 2022
Язык: Английский
Процитировано
94
Computational and Structural Biotechnology Journal, Год журнала: 2022, Номер 20, С. 6578 - 6585
Опубликована: Янв. 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.
Язык: Английский
Процитировано
93
Trends in Genetics, Год журнала: 2022, Номер 39(1), С. 74 - 88
Опубликована: Ноя. 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.
Язык: Английский
Процитировано
81
Molecular Biomedicine, Год журнала: 2023, Номер 4(1)
Опубликована: Авг. 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
Язык: Английский
Процитировано
72
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Март 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.
Язык: Английский
Процитировано
36
Pharmacological Research, Год журнала: 2023, Номер 194, С. 106840 - 106840
Опубликована: Июнь 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
Язык: Английский
Процитировано
38
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Окт. 27, 2023
Abstract Cardiovascular disease (CVD) is the leading cause of death in world, with a high incidence and youth-oriented tendency. RNA modification ubiquitous indispensable cell, maintaining cell homeostasis function by dynamically regulating gene expression. Accumulating evidence has revealed role aberrant expression CVD caused dysregulated modification. In this review, we focus on nine common modifications: N 6 -methyladenosine (m A), 1 5-methylcytosine 5 C), 7 -methylguanosine G), 4 -acetylcytosine (ac pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, modifications U34 tRNA wobble. We summarize key regulators their effects expression, such as splicing, maturation, transport, stability, translation. Then, based classification CVD, mechanisms which occurs progresses through are discussed. Potential therapeutic strategies, therapy, reviewed these mechanisms. Herein, some (such stroke peripheral vascular disease) not included due to limited availability literature. Finally, prospective applications challenges discussed for purpose facilitating clinical Moreover, look forward more studies exploring roles future, there substantial uncultivated areas be explored.
Язык: Английский
Процитировано
33