The impact of epitranscriptomic modifications on liver disease

Discovery of impacts of RNA modifications in liver disease has accelerated recently, with research on N6-methyladenosine and 5-methylcytosine proving particularly fruitful.These findings have yielded potential biomarkers and therapeutics to inform prognosis and course of treatment for hepatocellular...

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Veröffentlicht in:Trends in endocrinology and metabolism 2024-04, Vol.35 (4), p.331-346
Hauptverfasser: Berggren, Keith A., Schwartz, Robert E., Kleiner, Ralph E., Ploss, Alexander
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Sprache:eng
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Zusammenfassung:Discovery of impacts of RNA modifications in liver disease has accelerated recently, with research on N6-methyladenosine and 5-methylcytosine proving particularly fruitful.These findings have yielded potential biomarkers and therapeutics to inform prognosis and course of treatment for hepatocellular carcinoma and metabolic-associated steatohepatitis, and are likely to continue to yield results for other liver diseases.Despite these advances, a full mechanistic understanding of RNA modifications has been slow to advance owing to experimental limitations and the outsized impact of low levels of RNA modification.Both mechanistic studies looking at specific RNA modification sites and broad multi-omic studies using patient samples should be continued, with each type of study potentially informing the other and leading to novel insights into mechanisms and alternative effects of RNA-modifying enzymes and RNA modifications. RNA modifications have emerged as important mechanisms of gene regulation. Developmental, metabolic, and cell cycle regulatory processes are all affected by epitranscriptomic modifications, which control gene expression in a dynamic manner. The hepatic tissue is highly metabolically active and has an impressive ability to regenerate after injury. Cell proliferation, differentiation, and metabolism, which are all essential to the liver response to injury and regeneration, are regulated via RNA modification. Two such modifications, N6-methyladenosine (m6A)and 5-methylcytosine (m5C), have been identified as prognostic disease markers and potential therapeutic targets for liver diseases. Here, we describe progress in understanding the role of RNA modifications in liver biology and disease and discuss specific areas where unexpected results could lead to improved future understanding. RNA modifications have emerged as important mechanisms of gene regulation. Developmental, metabolic, and cell cycle regulatory processes are all affected by epitranscriptomic modifications, which control gene expression in a dynamic manner. The hepatic tissue is highly metabolically active and has an impressive ability to regenerate after injury. Cell proliferation, differentiation, and metabolism, which are all essential to the liver response to injury and regeneration, are regulated via RNA modification. Two such modifications, N6-methyladenosine (m6A)and 5-methylcytosine (m5C), have been identified as prognostic disease markers and potential therapeutic targets for
ISSN:1043-2760
1879-3061
1879-3061
DOI:10.1016/j.tem.2023.12.007