Identification of dynamic RNA-binding proteins uncovers a Cpeb4-controlled regulatory cascade during pathological

Eva Riechert1, Vivien Kmietczyk1, Frank Stein2

  • 1Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Germany.

Cell Reports
|May 12, 2021
PubMed

Insights

This study identifies 67 RNA-binding proteins (RBPs) in cardiomyocytes, revealing cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) as a key regulator of cardiac growth and remodeling by controlling specific mRNA targets.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Gene Regulation

Background:

  • RNA-binding proteins (RBPs) are crucial for cardiomyocyte function.
  • The specific RBPs involved in cardiac growth responses remain largely uncharacterized.

Purpose of the Study:

  • To comprehensively identify RBPs in healthy and diseased cardiomyocytes.
  • To investigate the role of cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) in cardiac growth and remodeling.

Main Methods:

  • RNA interactome capture was employed to identify RBPs.
  • In vitro and in vivo models were used to study Cpeb4 function.
  • mRNA targets of Cpeb4 were identified and validated.

Main Results:

  • 67 cardiomyocyte-specific RBPs were identified, including contractile proteins.
  • Cpeb4 was identified as a dynamic RBP regulating cardiac growth.
  • Cpeb4 regulates cardiac remodeling by controlling the expression of transcription factors Zeb1 and Zbtb20.

Conclusions:

  • Cpeb4 is a critical regulator of cardiomyocyte function during pathological growth.
  • Cpeb4 controls cardiac remodeling through differential mRNA binding and subsequent gene expression changes.

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