Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress

Yoshiaki Morishita, Hiroshi Arima, Maiko Hiroi, Masayuki Hayashi, Daisuke Hagiwara, Naoya Asai, Nobuaki Ozaki, Yoshihisa Sugimura, Hiroshi Nagasaki, Akira Shiota, Masahide Takahashi, Yutaka Oiso

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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 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.

Original languageEnglish
Pages (from-to)4846-4855
Number of pages10
JournalEndocrinology
Volume152
Issue number12
DOIs
Publication statusPublished - 01-12-2011

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Posterior Pituitary Hormones
Endoplasmic Reticulum Stress
Neurogenic Diabetes Insipidus
Arginine Vasopressin
Messenger RNA
Polyuria
Supraoptic Nucleus
Endoplasmic Reticulum
Vasotocin
Polydipsia
Tunicamycin
Protein Unfolding
Mutation
Thapsigargin
Vasopressins
Genes
Parturition
RNA
Neurons

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Morishita, Y., Arima, H., Hiroi, M., Hayashi, M., Hagiwara, D., Asai, N., ... Oiso, Y. (2011). Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. Endocrinology, 152(12), 4846-4855. https://doi.org/10.1210/en.2011-1415
Morishita, Yoshiaki ; Arima, Hiroshi ; Hiroi, Maiko ; Hayashi, Masayuki ; Hagiwara, Daisuke ; Asai, Naoya ; Ozaki, Nobuaki ; Sugimura, Yoshihisa ; Nagasaki, Hiroshi ; Shiota, Akira ; Takahashi, Masahide ; Oiso, Yutaka. / Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. In: Endocrinology. 2011 ; Vol. 152, No. 12. pp. 4846-4855.
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Morishita, Y, Arima, H, Hiroi, M, Hayashi, M, Hagiwara, D, Asai, N, Ozaki, N, Sugimura, Y, Nagasaki, H, Shiota, A, Takahashi, M & Oiso, Y 2011, 'Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress', Endocrinology, vol. 152, no. 12, pp. 4846-4855. https://doi.org/10.1210/en.2011-1415

Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. / Morishita, Yoshiaki; Arima, Hiroshi; Hiroi, Maiko; Hayashi, Masayuki; Hagiwara, Daisuke; Asai, Naoya; Ozaki, Nobuaki; Sugimura, Yoshihisa; Nagasaki, Hiroshi; Shiota, Akira; Takahashi, Masahide; Oiso, Yutaka.

In: Endocrinology, Vol. 152, No. 12, 01.12.2011, p. 4846-4855.

Research output: Contribution to journalArticle

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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 - 2011/12/1

Y1 - 2011/12/1

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.

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Morishita Y, Arima H, Hiroi M, Hayashi M, Hagiwara D, Asai N et al. Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. Endocrinology. 2011 Dec 1;152(12):4846-4855. https://doi.org/10.1210/en.2011-1415