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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 ? 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 ? cells.

SUBMITTER: Lee EK

PROVIDER: S-EPMC3319250 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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RNA-binding protein HuD controls insulin translation.

Lee Eun Kyung EK Kim Wook W Tominaga Kumiko K Martindale Jennifer L JL Yang Xiaoling X Subaran Sarah S SS Carlson Olga D OD Mercken Evi M EM Kulkarni Rohit N RN Akamatsu Wado W Okano Hideyuki H Perrone-Bizzozero Nora I NI de Cabo Rafael R de Cabo Rafael R Egan Josephine M JM Gorospe Myriam M

Molecular cell 20120301 6

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, H ...[more]

PMID: 22387028

Dataset Information

RNA-binding protein HuD controls insulin translation.

Publications

RNA-binding protein HuD controls insulin translation.

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