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Transcriptional coactivator PGC-1α contains a novel CBP80-binding motif that orchestrates efficient target gene

Hana Cho1,2, Xavier Rambout1,2, Michael L Gleghorn1,2,3

  • 1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.

Genes & Development
|April 15, 2018
PubMed

Insights

Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) uses a newly found motif to bind cap-binding protein 80 (CBP80). This interaction is crucial for gene expression and muscle cell differentiation.

Area of Science:

  • Molecular biology
  • Cellular metabolism
  • Transcriptional regulation

Background:

  • Peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α) is a key regulator of cellular metabolic adaptation.
  • The precise molecular mechanisms underlying PGC-1α's function as a transcriptional coactivator are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism of PGC-1α's transcriptional coactivation.
  • To identify novel protein-protein interactions involving PGC-1α.

Main Methods:

  • In vitro binding assays
  • X-ray crystallography
  • Immunoprecipitation of mouse myoblast cell lysates
  • RNA sequencing

Main Results:

  • A novel cap-binding protein 80 (CBP80)-binding motif (CBM) was identified in the C terminus of PGC-1α.
  • The CBM, an α helix, is essential for PGC-1α's association with CBP80 at the 5' cap of target transcripts.
  • PGC-1α CBM promotes RNA synthesis from promyogenic genes, as shown by RNA sequencing.

Conclusions:

  • A new link between DNA-associated and RNA-associated proteins was discovered, involving a cap-binding protein surveillance mechanism.
  • This mechanism, mediated by the PGC-1α CBM and CBP80 interaction, is vital for efficient myoblast differentiation into myotubes.
Keywords:
CBP80PGC-1αcap-binding complexgene transcriptionmyogenesispre-mRNP quality control

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