RNA Modification in Metabolism

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and most prevalent modification N6‐methyladenosine (m 6 A). Recently, emerged as a potential target for treatment. posttranscriptional gene expression that involved both physiological pathological processes. Evidence suggests m A significantly affects metabolism, its abnormal changes have observed variety diseases. Metabolic diseases are series caused by metabolic processes body, common include diabetes mellitus, obesity, nonalcoholic fatty liver disease, etc.; although pathogenesis these differs from each other to current understanding, recent studies suggested pivotal role modulating diseases, A‐based drug on agenda. This paper reviewed understanding hoping provide systematic information those area.

Language: Английский

Epitranscriptomic regulation of HIF-1: bidirectional regulatory pathways

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: March 18, 2025

Abstract Background Epitranscriptomics, the study of RNA modifications such as N 6 -methyladenosine (m A), provides a novel layer gene expression regulation with implications for numerous biological processes, including cellular adaptation to hypoxia. Hypoxia-inducible factor-1 (HIF-1), master regulator response low oxygen, plays critical role in adaptive and pathological cancer, ischemic heart disease, metabolic disorders. Recent discoveries accent dynamic interplay between m A HIF-1 signaling, revealing complex bidirectional regulatory network. While roles other remain largely unexplored, emerging evidence suggests their potential significance. Main body This review examines reciprocal epitranscriptomic machinery, writers, readers, erasers. modulates key components, while its own mRNA is regulated by modifications, positioning both target this system. interaction enhances our understanding hypoxic responses opens avenues clinical applications treating conditions like cancer disease. Promising progress has been made developing selective inhibitors targeting A-HIF-1 axis. However, challenges off-target effects complexity modification dynamics significant barriers translation. Conclusion The intricate highlights epitranscriptomics hypoxia-driven processes. Further research into these networks could drive therapeutic innovation hypoxia-related conditions. Overcoming specificity will be essential realizing therapies.

Language: Английский

FTO controls CD8+ T cell survival and effector response by modulating m6A methylation of Fas

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Abstract Functional CD8 + T cell immunity is essential for immune surveillance and host defense against infection tumors. Epigenetic mechanisms, particularly RNA modification, in controlling response not fully elucidated. Here, by cell-specific deletion of fat mass obesity-associated protein (FTO), a critical N6-methyladenosine (m 6 A) demethylase, we revealed that FTO was indispensable adequate protective function. ablation led to considerable death activated cells, which attributed apoptosis. MeRIP-seq analysis an increase m A methylation on Fas mRNA FTO-deficient cells. The loss promoted expression via enhancing the stability, depended reader insulin-like growth factor-2 mRNA-biding proteins 3 (IGF2BP3). Mutation sites or knockdown IGF2BP3 could normalize upregulated apoptosis levels caused Our findings delineate novel epigenetic regulatory mechanism FTO-mediated modification supporting survival effector responses, providing new insights into understanding post-transcriptional regulation immunological functions potential therapeutic intervention.

Language: Английский