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Expression of human BRE in multiple isoforms.

A K Ching1, P S Li, Q Li

  • 1Clinical Immunology Unit and Sir YK Pao Centre for Cancer, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

Biochemical and Biophysical Research Communications
|October 26, 2001
PubMed
Summary
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The BRE gene expresses multiple mRNA isoforms in human cells, with some potentially regulating stress responses. These isoforms show varying expression levels in normal versus immortalized cells and in response to stimuli.

Area of Science:

  • Molecular biology
  • Cell biology
  • Genetics

Background:

  • The BRE gene is implicated in modulating stress responses, specifically down-regulating TNF-alpha-induced NF-kappaB activation.
  • Alternative splicing is a key mechanism generating diverse mRNA transcripts from a single gene.

Purpose of the Study:

  • To investigate the expression of multiple mRNA isoforms of the BRE gene in human cells.
  • To characterize the predicted protein products and expression patterns of these BRE isoforms.

Main Methods:

  • Analysis of cDNA sequences to predict protein products of BRE isoforms.
  • Examination of BRE isoform expression across various human cell types, including normal and immortalized cell lines.
  • Investigating BRE isoform expression changes in peripheral blood monocytes and THP-1 cells upon lipopolysaccharide (LPS) stimulation.

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Main Results:

  • Six predominant mRNA isoforms of the BRE gene were identified, generated by alternative splicing.
  • Three isoforms (alpha(a), alpha(b), alpha(c)) encode BRE proteins with distinct C-termini, while three others (beta(a), beta(b), beta(c)) may be nonfunctional.
  • All examined human cells coexpress multiple BRE isoforms, with higher overall BRE expression in immortalized cell lines compared to normal cells.
  • LPS stimulation down-regulated all BRE isoforms in peripheral blood monocytes, with a less pronounced effect in THP-1 cells.
  • Isoform alpha(a), encoding the canonical BRE with a peroxisomal targeting sequence, was the most abundant transcript.

Conclusions:

  • The BRE gene is expressed as multiple mRNA isoforms in human cells, generated through alternative splicing.
  • Differential expression patterns of BRE isoforms are observed in normal versus immortalized cells and in response to inflammatory stimuli.
  • The canonical BRE isoform (alpha(a)) contains a peroxisomal targeting sequence, suggesting a role in regulating peroxisomal activities.