E. Lalli et al., Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA, MOL CELL B, 20(13), 2000, pp. 4910-4921
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.