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An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
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A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic β cells
Mark Li1,2,3, Fan Shao1,4,5, Qingwen Qian1,2,3
1Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
Molecular Therapy. Nucleic Acids
|September 13, 2021
Summary
Newly discovered micropeptides from long noncoding RNAs (lncRNAs) regulate pancreatic beta cell function. Beta cell and neural cell-regulin (BNLN) enhances insulin secretion, offering potential therapeutic targets for diabetes.
Area of Science:
- Molecular Biology
- Endocrinology
- Genomics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized as sources of functional micropeptides.
- Micropeptides play crucial roles in various biological processes, including metabolic regulation.
- The role of lncRNA-encoded micropeptides in pancreatic beta cell function remains largely unexplored.
Purpose of the Study:
- To identify and characterize micropeptides encoded by lncRNAs in the human pancreas.
- To investigate the function of a novel micropeptide, beta cell- and neural cell-regulin (BNLN), in pancreatic beta cells.
- To assess the impact of BNLN on insulin secretion and its relevance in diet-induced obesity and diabetes.
Main Methods:
- Computational identification of micropeptides from human pancreatic lncRNAs.
- Experimental verification and characterization of the BNLN micropeptide.
- Overexpression studies in pancreatic beta cells and analysis of ER calcium homeostasis and insulin secretion.
- Assessment of BNLN expression in mouse and human islets under different dietary conditions.
Main Results:
- Identified a novel 48-amino acid micropeptide, BNLN, encoded by the lncRNA TUNAR.
- BNLN localizes to the endoplasmic reticulum in pancreatic beta cells and regulates ER calcium levels.
- Overexpression of BNLN enhances glucose-stimulated insulin secretion and maintains ER homeostasis.
- BNLN expression is suppressed in diet-induced obesity, and its overexpression improves insulin secretion in lean, obese, and human islets.
Conclusions:
- lncRNA-encoded micropeptides, exemplified by BNLN, are critical regulators of pancreatic beta cell function.
- BNLN plays a significant role in maintaining beta cell function and insulin secretion, suggesting its involvement in diabetes pathophysiology.
- This study establishes a foundation for further research into micropeptide functions and their therapeutic potential in metabolic diseases like diabetes.
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