
RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure.
Heart performance relies on highly coordinated excitation-contraction (EC) coupling, and defects in this critical process may be exacerbated by additional genetic defects and/or environmental insults to cause eventual heart failure. Here we report a regulatory pathway consisting of the RNA binding protein RBFox2, a stress-induced microRNA miR-34a, and the essential EC coupler JPH2. In this pathway, initial cardiac defects diminish RBFox2 expression, which induces transcriptional repression of miR-34a, and elevated miR-34a targets Jph2 to impair EC coupling, which further manifests heart dysfunction, leading to progressive heart failure. The key contribution of miR-34a to this process is further established by administrating its mimic, which is sufficient to induce cardiac defects, and by using its antagomir to alleviate RBFox2 depletion-induced heart dysfunction. These findings elucidate a potential feed-forward mechanism to account for a critical transition to cardiac decompensation and suggest a potential therapeutic avenue against heart failure.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- RNA Splicing Factors
- Myocytes, Cardiac
- Muscle Proteins
- MicroRNAs
- Mice, Knockout
- Mice
- Membrane Proteins
- Humans
- Heart Failure
- Heart
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- RNA Splicing Factors
- Myocytes, Cardiac
- Muscle Proteins
- MicroRNAs
- Mice, Knockout
- Mice
- Membrane Proteins
- Humans
- Heart Failure
- Heart