The mechanical regulation of RNA binding protein hnRNPC in the failing heart

F Martino; NM Varadarajan; AR Perestrelo; V Hejret; H Durikova; D Vukic; V Horvath; F Cavalieri; F Caruso; WS Albihlal; AP Gerber; MA O'Connell; S Vanacova; S Pagliari; G Forte

Journal article

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

F Martino, NM Varadarajan, AR Perestrelo, V Hejret, H Durikova, D Vukic, V Horvath, F Cavalieri, F Caruso, WS Albihlal, AP Gerber, MA O'Connell, S Vanacova, S Pagliari, G Forte

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2022

DOI: 10.1126/scitranslmed.abo5715

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Abstract

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by reexpressing fetal contractile proteins via transcriptional and posttranscriptional processes, such as alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is up-regulated and relocates to the sarcomeric Z-disc upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates with the translation machinery. Alterations in hnRNPC expression, phosphorylation, and localization can..

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University of Melbourne Researchers

Francesca Cavalieri Author

Frank Caruso Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

F.M. was supported by the European Regional Development Fund-Project ENOCH (no. CZ.02.1.01/0.0/0.0/16_019/0000868). A.R.P., G.F., and S.P. were supported by the European Social Fund and European Regional Development Fund-Project MAGNET (CZ.02.1.01/0.0/0.0/15_003/0000492). F. Caruso acknowledges the award of a National Health and Medical Research Council Senior Principal Research Fellowship (GNT1135806). F. Cavalieri acknowledges the award of an Australian Research Council (ARC) Future Fellowship scheme (FT140100873) and the European Union's Horizon 2020 Research and Innovation Program under grant agreement no. 690901 (NANOSUPREMI). W.S.A. and A.P.G. were supported by the BBSRC (BB/N008820/1) and a Royal SocietyWolfson Research Merit Award (WM170036) to A.P.G. S.V. and N.M.V. were supported by the Czech Science Foundation (20-19617S) and the institutional support CEITEC 2020 (LQ1601). D.V. was supported by GACR 20-11101S. M.A.O. was supported by the Ministry of Education, Youth, and Sports within programme INTER-COST (LTC18052).