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Detection of RNA-binding Proteins by In Vitro RNA Pull-down in Adipocyte Culture
Published on: July 22, 2016
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.
Abstract:
The liver holds central roles in detoxification, energy metabolism, and whole body homeostasis but can develop malignant phenotypes when being chronically overwhelmed with fatty acids and glucose. The global rise of metabolic dysfunction-associated fatty liver disease (MAFLD) is already affecting a quarter of the global population. Pharmaceutical treatment options against different stages of MAFLD do not yet exist, and several clinical trials against hepatic transcription factors and other proteins have failed. However, emerging roles of noncoding RNAs, including long (lncRNA) and short noncoding RNAs (sRNA), in various cellular processes pose exciting new avenues for treatment interventions. Actions of noncoding RNAs mostly rely on interactions with proteins, whereby the noncoding RNA fine-tunes protein function in a process termed riboregulation. The developmental stage-, disease stage-, and cell type-specific nature of noncoding RNAs harbors enormous potential to precisely target certain cellular pathways in a spatiotemporally defined manner. Proteins interacting with RNAs can be categorized into canonical or noncanonical RNA-binding proteins (RBPs) depending on the existence of classical RNA-binding domains. Both, RNA- and RBP-centric methods have generated new knowledge of the RNA-RBP interface and added an additional regulatory layer. In this review, we summarize recent advances in how RBP-lncRNA interactions and various sRNAs shape cellular physiology and the development of liver diseases such as MAFLD and hepatocellular carcinoma.
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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