Noncoding RNAs and RNA-binding proteins: emerging governors of liver physiology and metabolic diseases

Christian Sommerauer1, Claudia Kutter1

  • 1Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Science for Life Laboratory, Stockholm, Sweden.

Insights

Noncoding RNAs, like long (lncRNA) and short (sRNA) RNAs, offer promising therapeutic targets for metabolic dysfunction-associated fatty liver disease (MAFLD). Their interactions with RNA-binding proteins (RBPs) provide precise control over cellular pathways, opening new treatment avenues.

Area of Science:

  • Molecular biology
  • Hepatology
  • Genomics

Background:

  • The liver is crucial for homeostasis but susceptible to metabolic overload, leading to fatty liver disease (MAFLD).
  • MAFLD affects a quarter of the global population, with limited pharmaceutical treatments available.
  • Current therapeutic strategies targeting hepatic proteins have shown limited success.

Purpose of the Study:

  • To review the emerging roles of noncoding RNAs (ncRNAs) in liver physiology and disease.
  • To explore the potential of ncRNA-protein interactions for MAFLD and hepatocellular carcinoma (HCC) treatment.
  • To highlight the spatiotemporal and cell-type specificity of ncRNAs for targeted interventions.

Main Methods:

  • Review of recent advances in RNA-centric and RNA-binding protein (RBP)-centric research.
  • Analysis of studies investigating RBP-lncRNA interactions and small noncoding RNAs (sRNAs).
  • Synthesis of knowledge on the RNA-RBP interface in cellular regulation.

Main Results:

  • Noncoding RNAs, including long noncoding RNAs (lncRNAs) and short noncoding RNAs (sRNAs), play significant roles in cellular processes.
  • Riboregulation, the fine-tuning of protein function by ncRNAs, offers precise control over cellular pathways.
  • RBP-lncRNA interactions and sRNAs are critical in shaping liver cell physiology and the pathogenesis of MAFLD and HCC.

Conclusions:

  • Noncoding RNAs represent a promising frontier for developing novel therapeutic strategies against liver diseases.
  • The specific nature of ncRNAs allows for targeted interventions in a spatiotemporally defined manner.
  • Understanding RNA-RBP interactions is key to unlocking new treatment modalities for MAFLD and HCC.

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