Androgen regulates the level and subcellular distribution of the AU-rich ribonucleic acid-binding protein HuR both in vitro and in vivo.
HuR, a member of the ELAV family of AU-rich RNA-binding proteins, is present in a variety of tissues and is directly involved in stabilizing labile AU-rich messenger RNAS: We have found that treating the human HepG2 cell line with 10 nM dihydrotestosterone (DHT) for 48 h decreases the total level of HuR by 75%. DHT decreases both cytosolic and nuclear HuR levels in HepG2 cells, but increases HuR levels in polyribosomes by 325%. In BALB/c mice, HuR levels in the submaxillary salivary gland (SMG) and the kidney display a dramatic sexual dimorphism, but those in the spleen and thyroid do not. DHT (200 microg) causes total HuR levels in female SMG and kidney to fall progressively, whereas, conversely, orchiectomy of males causes HuR levels to rise in these two tissues by 800% and 200%, respectively. As an internal control we probed the same blots for AUF1, a destabilizing AU-binding protein, and confirmed our previous findings showing that the cytosolic p37 isoform of AUF1 shows the opposite responses of cytosolic HuR in the SMG, and that the level of AUF1 in the kidney does not respond to DHT. In polyribosomes from female mouse SMG, HuR levels doubled after 6 h of DHT, but decreased by 80% after 24- and 48-h DHT treatment. Thus, the total level of HuR is regulated in two different androgen-responsive systems, as is the shuttling of HuR between different subcellular compartments. As AUF1 is responsive to androgen in the mouse SMG, but not in the kidney, tissue-specific posttranscriptional regulation of AU-rich messenger RNA metabolism could be mediated in part by differential androgen-dependent regulation of HuR and AUF1.
Sheflin
L G
LG
Department of Medicine, State University of New York and Veterans Affairs Western New York Healthcare System, Buffalo, New York 14215, USA.
Zhang
W
W
Spaulding
S W
SW
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000954:Antigens, Surface; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy; D009928:Organ Specificity; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis* / Q000378:metabolism*; D012727:Sex Characteristics; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D016601:RNA-Binding Proteins; D013196:Dihydrotestosterone