RNA-Binding Protein HuD Controls Insulin Translation

Eun Kyung Lee; Wook Kim; Kumiko Tominaga; Jennifer L. Martindale; Xiaoling Yang; Sarah S. Subaran; Olga D. Carlson; Evi M. Mercken; Rohit N. Kulkarni; Wado Akamatsu; Hideyuki Okano; Nora I. Perrone-Bizzozero; Rafael de Cabo; Josephine M. Egan; Myriam Gorospe

doi:10.1016/j.molcel.2012.01.016

RNA-Binding Protein HuD Controls Insulin Translation

Eun Kyung Lee, Wook Kim, Kumiko Tominaga, Jennifer L. Martindale, Xiaoling Yang, Sarah S. Subaran, Olga D. Carlson, Evi M. Mercken, Rohit N. Kulkarni, Wado Akamatsu, Hideyuki Okano, Nora I. Perrone-Bizzozero, Rafael de Cabo, Josephine M. Egan, Myriam Gorospe

Department of Physiology

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

Abstract

Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (. Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells.

Original language	English
Pages (from-to)	826-835
Number of pages	10
Journal	Molecular Cell
Volume	45
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2012.01.016
Publication status	Published - 2012 Mar 30

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2012.01.016

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@article{d07c1e988c264fd28b2e1277418c3ffe,

title = "RNA-Binding Protein HuD Controls Insulin Translation",

abstract = "Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (. Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells.",

author = "Lee, {Eun Kyung} and Wook Kim and Kumiko Tominaga and Martindale, {Jennifer L.} and Xiaoling Yang and Subaran, {Sarah S.} and Carlson, {Olga D.} and Mercken, {Evi M.} and Kulkarni, {Rohit N.} and Wado Akamatsu and Hideyuki Okano and Perrone-Bizzozero, {Nora I.} and {de Cabo}, Rafael and Egan, {Josephine M.} and Myriam Gorospe",

note = "Funding Information: We thank H.J. Okano, M. Igarashi, R. Selimyan, D. Nines, and D. Boyer for assistance and H. Huang for reagents. This work was supported in part by the National Institute on Aging-Intramural Research Program, National Institutes of Health (NIH). R.N.K. is supported by NIH grants RO1 DK 67536 and 68721. H.O. and W.A. are funded by the Japanese Ministry of Education, Science, Sports, Culture and Technology. E.K.L. is funded by the Korean Ministry of Education, Science and Technology (5-2011-A0154-00046). ",

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doi = "10.1016/j.molcel.2012.01.016",

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T1 - RNA-Binding Protein HuD Controls Insulin Translation

AU - Lee, Eun Kyung

AU - Kim, Wook

AU - Tominaga, Kumiko

AU - Martindale, Jennifer L.

AU - Yang, Xiaoling

AU - Subaran, Sarah S.

AU - Carlson, Olga D.

AU - Mercken, Evi M.

AU - Kulkarni, Rohit N.

AU - Akamatsu, Wado

AU - Okano, Hideyuki

AU - Perrone-Bizzozero, Nora I.

AU - de Cabo, Rafael

AU - Egan, Josephine M.

AU - Gorospe, Myriam

N1 - Funding Information: We thank H.J. Okano, M. Igarashi, R. Selimyan, D. Nines, and D. Boyer for assistance and H. Huang for reagents. This work was supported in part by the National Institute on Aging-Intramural Research Program, National Institutes of Health (NIH). R.N.K. is supported by NIH grants RO1 DK 67536 and 68721. H.O. and W.A. are funded by the Japanese Ministry of Education, Science, Sports, Culture and Technology. E.K.L. is funded by the Korean Ministry of Education, Science and Technology (5-2011-A0154-00046).

PY - 2012/3/30

Y1 - 2012/3/30

N2 - Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (. Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells.

AB - Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (. Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells.

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RNA-Binding Protein HuD Controls Insulin Translation

Abstract

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