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

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63 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 languageEnglish
Pages (from-to)826-835
Number of pages10
JournalMolecular Cell
Volume45
Issue number6
DOIs
Publication statusPublished - 2012 Mar 30

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lee, E. K., Kim, W., Tominaga, K., Martindale, J. L., Yang, X., Subaran, S. S., Carlson, O. D., Mercken, E. M., Kulkarni, R. N., Akamatsu, W., Okano, H., Perrone-Bizzozero, N. I., de Cabo, R., Egan, J. M., & Gorospe, M. (2012). RNA-Binding Protein HuD Controls Insulin Translation. Molecular Cell, 45(6), 826-835. https://doi.org/10.1016/j.molcel.2012.01.016