TY - JOUR
T1 - Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress
AU - Morishita, Yoshiaki
AU - Arima, Hiroshi
AU - Hiroi, Maiko
AU - Hayashi, Masayuki
AU - Hagiwara, Daisuke
AU - Asai, Naoya
AU - Ozaki, Nobuaki
AU - Sugimura, Yoshihisa
AU - Nagasaki, Hiroshi
AU - Shiota, Akira
AU - Takahashi, Masahide
AU - Oiso, Yutaka
PY - 2011/12
Y1 - 2011/12
N2 - 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 hypothalamicAVP 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 andoxytocin 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.
AB - 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 hypothalamicAVP 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 andoxytocin 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.
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U2 - 10.1210/en.2011-1415
DO - 10.1210/en.2011-1415
M3 - Article
C2 - 21971157
AN - SCOPUS:82355163415
SN - 0013-7227
VL - 152
SP - 4846
EP - 4855
JO - Endocrinology
JF - Endocrinology
IS - 12
ER -