SMN deficiency inhibits endochondral ossification via promoting TRAF6-induced ubiquitination degradation of YBX1 in spinal muscular atrophy.

ABSTRACT: Survival of motor neuron (SMN) protein encoded by SMN1 gene, is the essential and ubiquitously expressed protein in all tissues. Prior studies demonstrated that SMN deficiency impaired bone development, but the underlying mechanism of abnormal endochondral ossification remains obscure. Here, we showed SMN is involved in hypertrophic chondrocytes differentiation through regulating RNA splicing and protein degradation via analyzing single cell RNA-sequencing data of hypertrophic chondrocytes. Of note, SMN loss induced dwarfism and delayed endochondral ossification in Smn1 depletion-severe spinal muscular atrophy (SMA) mouse model and Smn1 chondrocyte conditional knockdown mouse. Histological analysis revealed that SMN deficiency expanded the zone of hypertrophic chondrocytes in the growth pl

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC12665793 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature