Nsun4 and Mettl3 mediated translational reprogramming of Sox9 promotes BMSC chondrogenic differentiation.

ABSTRACT: The chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) has been used in the treatment and repair of cartilage defects; however, the in-depth regulatory mechanisms by which RNA modifications are involved in this process are still poorly understood. Here, we found that Sox9, a critical transcription factor that mediates chondrogenic differentiation, exhibited enhanced translation by ribosome sequencing in chondrogenic pellets, which was accompanied by increased 5-methylcytosine (m⁵C) and N6-methyladenosine (m⁶A) levels. Nsun4-mediated m⁵C and Mettl3-mediated m⁶A modifications were required for Sox9-regulated chondrogenic differentiation. Interestingly, we showed that in the 3'UTR of Sox9 mRNA, Nsun4 catalyzed the m

SUBMITTER: Yang L 

PROVIDER: S-EPMC9133052 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature