A rampant and urgent global health issue of the 21st century is the emergence and progression of fatty liver disease (FLD), including alcoholic fatty liver disease and the more heterogenous metabolism-associated (or non-alcoholic) fatty liver disease (MAFLD/NAFLD) phenotypes. These conditions manifest as disease spectra, progressing from benign hepatic steatosis to symptomatic steatohepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma. With numerous intricately regulated molecular pathways implicated in its pathophysiology, recent data have emphasized the critical roles of RNA-binding proteins (RBPs) in the onset and development of FLD. They regulate gene transcription and post-transcriptional processes, including pre-mRNA splicing, capping, and polyadenylation, as well as mature mRNA transport, stability, and translation. RBP dysfunction at every point along the mRNA life cycle has been associated with altered lipid metabolism and cellular stress response, resulting in hepatic inflammation and fibrosis. Here, we discuss the current understanding of the role of RBPs in the post-transcriptional processes associated with FLD and highlight the possible and emerging therapeutic strategies leveraging RBP function for FLD treatment. This article is categorized under: RNA in Disease and Development > RNA in Disease.
Keywords: NASH; RNA processing; R‐loops; hepatocellular dysfunction; liver cancer; liver cirrhosis; post‐transcriptional gene regulation.
© 2024 The Authors. WIREs RNA published by Wiley Periodicals LLC.