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Altered expressions and splicing profiles of Acin1 transcripts differentially modulate brown adipogenesis through an

Ying-Chin Lin1, Yi-Han Lu2, Yuan-Chii Lee3

  • 1Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms
|July 7, 2020
PubMed

Insights

Apoptotic chromatin condensation inducer in the nucleus (Acin1) regulates brown fat development. Its isoforms influence adipogenesis and splicing factor SRSF3 expression via alternative splicing, impacting thermogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Apoptotic chromatin condensation inducer in the nucleus (Acin1) is an RNA-binding protein and an exon junction complex (EJC) component.
  • Brown adipose tissues (BATs) are crucial for non-shivering thermogenesis, involving lipid consumption.

Purpose of the Study:

  • To investigate the role of Acin1 in brown adipose tissue (BAT) development and thermogenesis.
  • To explore the impact of Acin1 isoforms on adipogenesis and splicing regulation.

Main Methods:

  • Whole-transcriptome analyses were performed.
  • Expression levels and splicing profiles of Acin1 transcripts were analyzed during BAT development.
  • Acin1 isoform depletion and overexpression were conducted in mouse fibroblasts.
  • Alternative splicing-coupled nonsense-mediated decay mechanisms were investigated.

Main Results:

  • Reduced Acin1 expression and altered splicing profiles were observed during BAT development.
  • Depletion of Acin1 activated brown adipogenic signatures.
  • Acin1-L and Acin1-S isoforms differentially influenced brown adipogenesis and serine/arginine-rich splicing factor 3 (SRSF3) expression.
  • An Acin1-SRSF3 regulatory pathway within the brown adipocyte splicing network was identified.

Conclusions:

  • Acin1 plays a significant role in regulating brown adipogenesis and thermogenesis.
  • The interplay between EJC components and splicing regulators, like Acin1 and SRSF3, offers a novel mechanism for controlling brown adipogenesis through alternative splicing.
Keywords:
Acin1Alternative splicingBrown adipocyteC3H10T1/2SRSF3

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