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Updated: Sep 30, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
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Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease

Andrew M Jobbins1,2, Nejc Haberman1,2, Natalia Artigas1,2

  • 1MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, UK.

Nucleic Acids Research
|March 16, 2022
PubMed

Insights

Pre-mRNA processing alterations, particularly polyadenylation, are linked to non-alcoholic fatty liver disease (NAFLD). Decreased SRSF10 expression exacerbates metabolic dysfunction in NAFLD.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Metabolic Diseases

Background:

  • Pre-mRNA processing is crucial for gene expression and mRNA maturation in eukaryotes.
  • Defects in pre-mRNA processing are linked to diseases, but their role in metabolic pathologies remains unclear.
  • Non-alcoholic fatty liver disease (NAFLD) is a growing metabolic concern with complex underlying mechanisms.

Purpose of the Study:

  • To investigate the role of pre-mRNA processing, specifically alternative splicing and polyadenylation, in NAFLD.
  • To identify key regulatory factors involved in pre-mRNA dysregulation in NAFLD.
  • To explore the functional significance of SRSF10 in metabolic regulation and liver disease.

Main Methods:

  • Analysis of alternative splicing and polyadenylation patterns in NAFLD samples.
  • Assessment of Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding and expression.
  • Inactivation of SRSF10 in cellular and animal models of NAFLD.
  • Evaluation of metabolic gene polyadenylation and metabolic dysfunction.

Main Results:

  • Alternative splicing and polyadenylation are significantly altered in NAFLD.
  • SRSF10 expression is decreased in NAFLD, with its binding sites near polyadenylation signals.
  • SRSF10 inactivation dysregulates polyadenylation of metabolic genes like PPARA and worsens diet-induced metabolic dysfunction.
  • NAFLD models show altered polyadenylation of key metabolic genes.

Conclusions:

  • Dysregulated pre-mRNA polyadenylation is implicated in obesity-induced liver disease (NAFLD).
  • SRSF10 plays a novel and critical role in mediating pre-mRNA polyadenylation in liver metabolism.
  • Targeting SRSF10 or polyadenylation pathways may offer therapeutic strategies for NAFLD.

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