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RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure.

Publication ,  Journal Article
Hu, J; Gao, C; Wei, C; Xue, Y; Shao, C; Hao, Y; Gou, L-T; Zhou, Y; Zhang, J; Ren, S; Chen, J; Wang, Y; Fu, X-D
Published in: Proc Natl Acad Sci U S A
March 26, 2019

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 26, 2019

Volume

116

Issue

13

Start / End Page

6172 / 6180

Location

United States

Related Subject Headings

  • RNA Splicing Factors
  • Myocytes, Cardiac
  • Muscle Proteins
  • MicroRNAs
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Humans
  • Heart Failure
  • Heart
 

Citation

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Chicago
ICMJE
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Hu, J., Gao, C., Wei, C., Xue, Y., Shao, C., Hao, Y., … Fu, X.-D. (2019). RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure. Proc Natl Acad Sci U S A, 116(13), 6172–6180. https://doi.org/10.1073/pnas.1822176116
Hu, Jing, Chen Gao, Chaoliang Wei, Yuanchao Xue, Changwei Shao, Yajing Hao, Lan-Tao Gou, et al. “RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure.Proc Natl Acad Sci U S A 116, no. 13 (March 26, 2019): 6172–80. https://doi.org/10.1073/pnas.1822176116.
Hu J, Gao C, Wei C, Xue Y, Shao C, Hao Y, et al. RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6172–80.
Hu, Jing, et al. “RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure.Proc Natl Acad Sci U S A, vol. 116, no. 13, Mar. 2019, pp. 6172–80. Pubmed, doi:10.1073/pnas.1822176116.
Hu J, Gao C, Wei C, Xue Y, Shao C, Hao Y, Gou L-T, Zhou Y, Zhang J, Ren S, Chen J, Wang Y, Fu X-D. RBFox2-miR-34a-Jph2 axis contributes to cardiac decompensation during heart failure. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6172–6180.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 26, 2019

Volume

116

Issue

13

Start / End Page

6172 / 6180

Location

United States

Related Subject Headings

  • RNA Splicing Factors
  • Myocytes, Cardiac
  • Muscle Proteins
  • MicroRNAs
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Humans
  • Heart Failure
  • Heart