The Role of RNA Splicing in Liver Function and Disease: A Focus on Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

RNA splicing is an essential post-transcriptional mechanism that facilitates the excision of introns and the connection of exons to produce mature mRNA, which is essential for gene expression and proteomic diversity. In the liver, precise splicing regulation is critical for maintaining metabolic balance, detoxification, and protein synthesis. This review explores the mechanisms of RNA splicing and the role of splicing factors, particularly in the context of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This review also highlights how RNA splicing dysregulation can lead to aberrant splicing and impact the progression of liver diseases such as MASLD, with a particular focus on Metabolic Dysfunction-Associated Steatohepatitis (MASH), which represents the advanced stage of MASLD. Recent advances in the clinical application of antisense oligonucleotides (ASOs) to correct splicing errors offer promising therapeutic strategies for restoring normal liver function. Additionally, the dysregulation of splicing observed in liver diseases may serve as a potential diagnostic marker, offering new opportunities for early identification of individuals more susceptible to disease progression. This review provides insights into the molecular mechanisms that govern splicing regulation in the liver, with a particular emphasis on MASLD, and discusses potential therapeutic approaches targeting RNA splicing to treat MASLD and related metabolic disorders.