N⁶-Methyladenosine-mediated phase separation suppresses NOTCH1 expression and promotes mitochondrial fission in diabetic cardiac fibrosis.

ABSTRACT:

Background

N⁶-methyladenosine (m⁶A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m⁶A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive.

Methods

Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1^flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase

SUBMITTER: Liu ZY 

PROVIDER: S-EPMC11439301 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature