Posttranscriptional reprogramming controls MASLD progression through chronic ER stress adaptation - PubMed
19 hours ago
- #ER stress
- #MASLD
- #posttranscriptional regulation
- Chronic ER stress from a high-fat diet drives MASLD/MASH progression.
- Posttranscriptional regulation, not just transcription, controls ~70% of gene expression changes in MASLD.
- A subset of mRNAs with suboptimal codons and short poly(A) tails under normal diet are translationally activated by poly(A) tail elongation during chronic ER stress.
- These regulated mRNAs are linked to cell cycle, immune response, fibrosis, and tissue remodeling, correlating with MASH severity in mice and humans.
- The regulation is mediated by cis-elements in the 3' UTR coordinating polyadenylation and deadenylation.
- Loss of this adaptive posttranscriptional reprogramming worsens liver damage and increases tumor burden in mice.