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 receptor superfamily which acts as a transcriptional repressor. Mutations in the human DAX-1 gene cause X-linked adrenal hypoplasia congenita (AHC) associated with hypogonadotropic hypogonadism (HHG). We have studied the intracellular 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 significant proportion of DAX-1 is associated with polyribosomes and is found complexed with polyadenylated RNA. DAX-1 directly binds to RNA, two domains within the protein being responsible for cooperative binding activity and specificity. Mutations in DAX-1 found in AHC-HHG patients significantly impair RNA binding. These findings reveal that DAX-1 plays multiple regulatory roles at the transcriptional and posttranscriptional levels.
Lalli
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E
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université Louis Pasteur, Illkirch-Strasbourg, France.
Ohe
K
K
Hindelang
C
C
Sassone-Corsi
P
P
D000302:Adrenal Cortex / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D007985:Leydig Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009154:Mutation; D011061:Poly A / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D012097:Repressor Proteins; D012261:Ribonucleoproteins / Q000378:metabolism / Q000648:ultrastructure; D013696:Temperature; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; C539966:Nr0b1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; D011061:Poly A