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Hormone-dependent expression of a steroidogenic acute regulatory protein natural antisense transcript in MA-10 mouse

Ana Fernanda Castillo1, Jinjiang Fan, Vassilios Papadopoulos

  • 1Department of Human Biochemistry, School of Medicine, Instituto de Investigaciones Moleculares de Enfermedades Hormonales Neurodegenerativas y Oncológicas, University of Buenos Aires, Buenos Aires, Argentina.

Plos One
|August 11, 2011
PubMed

Insights

Researchers discovered a new natural antisense transcript (NAT) that regulates steroidogenic acute regulatory protein (StAR) expression. This antisense RNA impacts StAR protein levels and progesterone production, revealing a novel regulatory mechanism in steroid biosynthesis.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Gene Regulation

Background:

  • Cholesterol transport is crucial for steroidogenesis, regulated by the steroidogenic acute regulatory protein (StAR).
  • StAR is expressed via multiple transcripts differing in 3'-untranslated regions, suggesting post-transcriptional regulation.
  • Natural antisense transcripts (NATs) represent a layer of eukaryotic gene expression control.

Purpose of the Study:

  • To identify and characterize novel NATs regulating StAR expression.
  • To investigate the role of Star NAT in steroidogenesis and its regulation by human chorionic gonadotropin (hCG).
  • To elucidate the impact of Star NAT on StAR transcript levels, protein expression, and progesterone production.

Main Methods:

  • 5' and 3' RACE (Rapid Amplification of cDNA Ends)
  • Strand-specific RT-PCR (Reverse Transcription Polymerase Chain Reaction)
  • Ribonuclease protection assays
  • MA-10 Leydig cell culture and murine steroidogenic tissue analysis

Main Results:

  • A novel Star NAT complementary to spliced Star mRNA was identified and confirmed in MA-10 Leydig cells and murine steroidogenic tissues.
  • Human chorionic gonadotropin (hCG) stimulation via cAMP upregulates Star NAT expression.
  • Overexpression of Star NAT differentially affects Star sense transcripts and downregulates StAR protein and progesterone production.

Conclusions:

  • Antisense transcription represents an additional regulatory mechanism in steroid biosynthesis.
  • Co-expression and coordinate regulation of sense-antisense Star RNAs modulate steroidogenic pathways.
  • Star NAT plays a significant role in controlling StAR protein levels and steroid production.

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