Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA

The DAX-1 (NR0B1) gene encodes an unusual member of the nuclear hormone rec eptor superfamily which acts as a transcriptional repressor. Mutations in t he human DAX-1 gene cause X-linked adrenal hypoplasia congenita (AHC) assoc iated with hypogonadotropic hypogonadism (HHG). We have studied the intrace llular localization of the DAX-1 protein in human adrenal cortex and mouse Leydig tumor cells and found it to be both nuclear and cytoplasmic. A signi ficant proportion of DAX-1 is associated with polyribosomes and is found co mplexed with polyadenylated RNA. DAX-1 directly binds to RNA, two domains w ithin the protein being responsible for cooperative binding activity and sp ecificity. Mutations in DAX-1 found in AHC-HHG patients significantly impai r RNA binding. These findings reveal that DAX-1 plays multiple regulatory r oles at the transcriptional and posttranscriptional levels.