Lalli E, Ohe K, Hindelang C, Sassone-Corsi P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université Louis Pasteur, Illkirch-Strasbourg, France.
Mol Cell Biol. 2000 Jul;20(13):4910-21. doi: 10.1128/MCB.20.13.4910-4921.2000.
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.
DAX-1（NR0B1）基因编码核激素受体超家族中一个不同寻常的成员，该成员作为转录抑制因子发挥作用。人类DAX-1基因的突变会导致与促性腺激素功能减退性性腺功能减退（HHG）相关的X连锁先天性肾上腺发育不全（AHC）。我们研究了DAX-1蛋白在人肾上腺皮质和小鼠睾丸间质细胞瘤细胞中的细胞内定位，发现它既存在于细胞核中，也存在于细胞质中。相当一部分DAX-1与多核糖体相关，并发现它与聚腺苷酸化RNA结合。DAX-1直接与RNA结合，该蛋白内的两个结构域负责协同结合活性和特异性。在AHC-HHG患者中发现的DAX-1突变会显著损害RNA结合。这些发现揭示了DAX-1在转录和转录后水平发挥多种调节作用。
