FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis
Beijing Institute of Genomics · University of Chinese Academy of Sciences · +9 more institutions
Abstract
The role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adipogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5'- and 3'-splice sites, spatially overlapping with mRNA splicing regulatory serine/arginine-rich (SR) protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to…
Citation impact
- FWCI
- 17.78
- Percentile
- 100%
- References
- 68
Authors
27Topics & keywords
- Adipogenesis
- RNA splicing
- Demethylase
- Alternative splicing
- N6-Methyladenosine
- Cell biology
- Messenger RNA
- Exon