Cardiomyocyte‐specific Srsf3 deletion reveals a mitochondrial regulatory role. Issue 5 (5th April 2021)

• Record Type: Journal Article
• Authors: Dumont, Audrey‐Ann; Dumont, Lauralyne; Zhou, Delong; Giguère, Hugo; Pileggi, Chantal; Harper, Mary‐Ellen; Blondin, Denis P.; Scott, Michelle S.; Auger‐Messier, Mannix
• Is Part Of: FASEB journal. Volume 35:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-04-05
• Subjects: cardiomyocyte -- mitochondria -- oxidative phosphorylation -- respiratory chain complex I -- Srsf3; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002293RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Serine‐rich splicing factor 3 (SRSF3) was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte‐specific Srsf3 conditional knockout (cKO) mouse model. Fifteen‐day‐old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced the left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodeling induced by Srsf3 deletion. RNA‐seq analysis of the hearts of 5‐day‐old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I‐driven respiration of permeabilized cardiac muscle fibers from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating the mitochondrial integrity.