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Published on: July 15, 2025
RNA-binding protein HuD controls insulin translation
Eun Kyung Lee1, Wook Kim, Kumiko Tominaga
1Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
The RNA-binding protein HuD regulates insulin production in pancreatic beta cells. It binds to preproinsulin mRNA, controlling translation and insulin levels, especially after glucose stimulation.
Area of Science:
- Molecular biology
- Endocrinology
- Cell biology
Background:
- The RNA-binding protein HuD was previously thought to be exclusively expressed in neurons.
- Pancreatic beta cells are crucial for glucose homeostasis and insulin production.
Purpose of the Study:
- To investigate the role of HuD in pancreatic beta cells.
- To determine HuD's mechanism of action in regulating insulin production.
Main Methods:
- Investigated HuD expression in pancreatic beta cells.
- Analyzed HuD's interaction with preproinsulin (Ins2) mRNA using molecular biology techniques.
- Manipulated HuD levels in vitro and in vivo (HuD-knockout and overexpression mice).
- Assessed insulin translation and production under various conditions, including glucose stimulation.
Main Results:
- HuD is present and regulated by the insulin receptor pathway in pancreatic beta cells.
- HuD binds to the 5' untranslated region (UTR) of Ins2 mRNA.
- HuD overexpression inhibits insulin translation and production, while HuD silencing enhances them.
- Glucose treatment causes rapid dissociation of HuD from Ins2 mRNA, facilitating insulin biosynthesis.
- HuD-knockout mice show increased insulin levels, whereas HuD-overexpressing mice exhibit decreased insulin levels.
Conclusions:
- HuD is a novel and pivotal regulator of insulin translation in pancreatic beta cells.
- HuD acts as a negative regulator of insulin production, with its activity modulated by glucose.
- Understanding HuD's role offers potential therapeutic targets for diabetes and related metabolic disorders.
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