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A novel isoform of hydroxyacyl-CoA dehydrogenase inhibits cell proliferation

Guiyu Xia1, Yunyi Gao2, Canlan Wu2

  • 1Shaoxing Maternity and Child Health Care Hospital, Shaoxing, Zhejiang, 312000, China.

Biochemical and Biophysical Research Communications
|March 27, 2022
PubMed

Insights

Researchers discovered a new short form of hydroxyacyl-CoA dehydrogenase (HADH-S) that is located in the nucleus and affects cell proliferation. This finding reveals novel regulation of HADH in cellular processes.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Hydroxyacyl-CoA dehydrogenase (HADH) is crucial for mitochondrial beta-oxidation.
  • The regulatory mechanisms governing HADH expression and function are not fully understood.

Purpose of the Study:

  • To investigate the translational regulation and functional significance of HADH.
  • To identify novel isoforms of HADH and their roles in cellular processes.

Main Methods:

  • Quantitative translation initiation sequencing (QTI-seq) was employed to analyze HADH mRNA.
  • Overexpression studies were conducted in mouse embryonic fibroblasts.

Main Results:

  • Murine Hadh mRNA was found to possess two alternative translation start codons.
  • Translation from the upstream start codon yields the known mitochondrial HADH isoform.
  • Translation from the downstream start codon produces a novel short isoform (HADH-S) localized primarily in the nucleus.

Conclusions:

  • A novel HADH isoform, HADH-S, was identified with a distinct nuclear localization.
  • HADH-S overexpression inhibits the proliferation of mouse embryonic fibroblasts, suggesting a role in cell cycle regulation.
  • These findings uncover a new layer of HADH regulation impacting cell proliferation.

Keywords:
Alternative translation initiationCell proliferationHADHIsoform

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