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circGlis3 promotes β-cell dysfunction by binding to heterogeneous nuclear ribonucleoprotein F and encoding

Li Xiong1,2, Yingying Gong3, Huashan Liu1,2

  • 1Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Iscience
|January 16, 2024
PubMed

Insights

Circular RNAs (circRNAs) regulate β-cell function and are implicated in type 2 diabetes mellitus (T2DM). This study reveals circGlis3 impairs β-cell function by affecting protein interactions and gene expression, suggesting it as a T2DM therapeutic target.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are key regulators of pancreatic β-cell function.
  • Lipotoxicity-induced β-cell damage in type 2 diabetes mellitus (T2DM) involves circRNAs.
  • circGlis3, a circRNA from the Glis3 gene, is upregulated in lipotoxic β-cells, but its function is unknown.

Purpose of the Study:

  • To elucidate the functional role and molecular mechanism of circGlis3 in β-cell function.
  • To investigate the involvement of circGlis3 in T2DM pathogenesis.

Main Methods:

  • Investigated the biogenesis of circGlis3, facilitated by the splicing factor CUGBP Elav-Like Family Member 1 (CELF1).
  • Generated and analyzed a transgenic mouse model overexpressing circGlis3.
  • Examined the molecular interactions of circGlis3 with heterogeneous nuclear ribonucleoprotein F (hnRNPF) and GLIS3.

Main Results:

  • Overexpression of circGlis3 in a mouse model impaired β-cell function.
  • circGlis3 binds to hnRNPF, inhibiting its nuclear translocation and reducing Sirt1 levels.
  • circGlis3 encodes a protein that interacts with GLIS3, suppressing its transcriptional activity.

Conclusions:

  • circGlis3 plays a critical role in β-cell dysfunction.
  • circGlis3 may represent a potential therapeutic target for T2DM.
Keywords:
BiochemistryCell biologyMolecular biology

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