title: Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress.
abstract: Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of arginine vasopressin (AVP), an antidiuretic hormone. Although the carriers are normal at birth, polyuria and polydipsia appear several months or years later. Previously, we made mice possessing a mutation causing FNDI and reported that the mice manifested progressive polyuria as do the patients with FNDI. Here, we report that decreases in AVP mRNA expression in the supraoptic nucleus were accompanied by shortening of the AVP mRNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons. Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice. Incubation of hypothalamic explants of wild-type mice with ER stressors (thapsigargin and tunicamycin) caused shortening of the poly(A) tail length of AVP and oxytocin mRNA, accompanied by decreases in their expression. On the other hand, an ER stress-reducing molecule (tauroursodeoxycholate) increased the poly(A) tail length as well as the expression levels of AVP and oxytocin mRNA. These data reveal a novel mechanism by which ER stress decreases poly(A) tail length of neurohypophysial hormones, probably to reduce the load of unfolded proteins.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.forename: Maiko
authors.initials: M
authors.lastname: Hiroi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Shiota
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics; D059865:Endoplasmic Reticulum Stress; D051379:Mice; D010121:Oxytocin; D010909:Pituitary Hormones, Posterior / Q000378:metabolism*; D011061:Poly A / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013495:Supraoptic Nucleus / Q000378:metabolism
chemical_list: D010909:Pituitary Hormones, Posterior; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D011061:Poly A; D010121:Oxytocin