Frontiers in Genetics (Nov 2020)

A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling

  • Etienne Boileau,
  • Etienne Boileau,
  • Etienne Boileau,
  • Shirin Doroudgar,
  • Shirin Doroudgar,
  • Eva Riechert,
  • Eva Riechert,
  • Lonny Jürgensen,
  • Lonny Jürgensen,
  • Thanh Cao Ho,
  • Hugo A. Katus,
  • Hugo A. Katus,
  • Mirko Völkers,
  • Mirko Völkers,
  • Christoph Dieterich,
  • Christoph Dieterich,
  • Christoph Dieterich

DOI
https://doi.org/10.3389/fgene.2020.583124
Journal volume & issue
Vol. 11

Abstract

Read online

Our understanding of the transition from physiological to pathological cardiac hypertrophy remains elusive and largely based on reductionist hypotheses. Here, we profiled the translatomes of 15 mouse hearts to provide a molecular blueprint of altered gene networks in early cardiac remodeling. Using co-expression analysis, we showed how sub-networks are orchestrated into functional modules associated with pathological phenotypes. We discovered unappreciated hub genes, many undocumented for their role in cardiac hypertrophy, and genes in the transcriptional network that were rewired in the translational network, and associated with semantically different subsets of enriched functional terms, such as Fam210a, a novel musculoskeletal modulator, or Psmd12, implicated in protein quality control. Using their correlation structure, we found that transcriptome networks are only partially reproducible at the translatome level, providing further evidence of post-transcriptional control at the level of translation. Our results provide novel insights into the complexity of the organization of in vivo cardiac regulatory networks.

Keywords