Journal article
A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic β cells
Molecular therapy. Nucleic acids, Vol.26, pp.307-320
12/03/2021
DOI: 10.1016/j.omtn.2021.06.027
PMCID: PMC8416971
PMID: 34513312
Abstract
Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a β cell- and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA (TUNAR, also known as TUNA, HI-LNC78, or LINC00617). We named this highly conserved 48-amino-acid micropeptide beta cell- and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic β cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucose-stimulated insulin secretion in pancreatic β cells. We further assessed the BNLN expression in islets from mice fed a high-fat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic β cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.
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In this study, we identified one islet lncRNA, TUNAR, contains a sORF encoding for micropeptide BNLN. We further demonstrated that BNLN regulates insulin secretion in the pancreatic β cells in health and diseases. Our study provides important insights into the molecular mechanisms that underlie the fine-tuning of glucose-induced insulin secretion by translational function of lncRNA.
Details
- Title: Subtitle
- A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic β cells
- Creators
- Mark Li - University of IowaFan Shao - University of IowaQingwen Qian - University of IowaWenjie Yu - University of IowaZeyuan Zhang - Roy J. and Lucille A. Carver College of MedicineBiyi Chen - University of IowaDan Su - University of IowaYuwei Guo - University of IowaAn-Vi Phan - University of IowaLong-sheng Song - University of IowaSamuel B. Stephens - University of IowaJulien Sebag - University of IowaYumi Imai - University of IowaLing Yang - Roy J. and Lucille A. Carver College of MedicineHuojun Cao - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Nucleic acids, Vol.26, pp.307-320
- DOI
- 10.1016/j.omtn.2021.06.027
- PMID
- 34513312
- PMCID
- PMC8416971
- NLM abbreviation
- Mol Ther Nucleic Acids
- ISSN
- 2162-2531
- eISSN
- 2162-2531
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 12/03/2021
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Endodontics; Iowa Neuroscience Institute; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Dental Research; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984284353602771
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