AUTHOR=Boileau Etienne , Doroudgar Shirin , Riechert Eva , Jürgensen Lonny , Ho Thanh Cao , Katus Hugo A. , Völkers Mirko , Dieterich Christoph TITLE=A Multi-Network Comparative Analysis of Transcriptome and Translatome Identifies Novel Hub Genes in Cardiac Remodeling JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.583124 DOI=10.3389/fgene.2020.583124 ISSN=1664-8021 ABSTRACT=

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.