Conserved function of the long noncoding RNA Blnc1 in brown adipocyte differentiation
| Autor: | Lin Mi, Jiandie D. Lin, Siming Li, Gongshe Yang, Xu Yun Zhao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mutant Brown fat Heterogeneous-Nuclear Ribonucleoprotein U Blnc1 Cox7a1 cytochrome c oxidase subunit 7A1 Mice 0302 clinical medicine lncRNA Rapid amplification of cDNA ends Adipose Tissue Brown Gene expression EBF2 early B cell factor 2 Adipocytes Cells Cultured Genetics PRDM16 SDHB succinate dehydrogenase complex iron sulfur subunit B Thermogenesis Cell Differentiation Pparα peroxisome proliferator-activated receptor alpha Non-coding RNA Long non-coding RNA Adipocytes Brown RNA Recognition Motif Proteins Ribonucleoproteins RACE rapid amplification of cDNA ends Original Article RNA Long Noncoding Elovl3 elongation of very long chain fatty acids like 3 Prdm16 PR domain zinc finger protein 16 lcsh:Internal medicine Dio2 deiodinase iodothyronine type II PPARγ peroxisome proliferator-activated receptor gamma Brown adipocyte differentiation Biology ATP5A ATP synthase H+ transporting mitochondrial F1 complex alpha 1 03 medical and health sciences Animals Humans lcsh:RC31-1245 Molecular Biology Gene Ppargc1a peroxisome proliferator-activated receptor gamma coactivator 1-alpha EBF2 UQCRC2 ubiquinol-cytochrome c reductase core protein II RNA Cell Biology Ucp1 uncoupling protein 1 BAT brown adipose tissue 030104 developmental biology HEK293 Cells Gene Expression Regulation FABP4 fatty acid binding protein 4 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Molecular Metabolism, Vol 6, Iss 1, Pp 101-110 (2017) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Objective Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological processes. Recent work has demonstrated that the inducible lncRNA Blnc1 stimulates thermogenic gene expression during brown and beige adipocyte differentiation. However, whether Blnc1 is functionally conserved in humans has not been explored. In addition, the molecular basis of the Blnc1 ribonucleoprotein complex in thermogenic gene induction remains incompletely understood. The aims of the current study were to: i) investigate functional conservation of Blnc1 in mice and humans and ii) elucidate the molecular mechanisms by which Blnc1 controls the thermogenic gene program in brown adipocytes. Methods Full-length human Blnc1 was cloned and examined for its ability to stimulate brown adipocyte differentiation. Different truncation mutants of Blnc1 were generated to identify functional RNA domains responsible for thermogenic gene induction. RNA-protein interaction studies were performed to delineate the molecular features of the Blnc1 ribonucleoprotein complex. Results Blnc1 is highly conserved in mice and humans at the sequence and function levels, both capable of stimulating brown adipocyte gene expression. A conserved RNA domain was identified to be required and sufficient for the biological activity of Blnc1. We identified hnRNPU as an RNA-binding protein that facilitates the assembly and augments the transcriptional function of the Blnc1/EBF2 ribonucleoprotein complex. Conclusions Blnc1 is a conserved lncRNA that promotes thermogenic gene expression in brown adipocytes through formation of the Blnc1/hnRNPU/EBF2 ribonucleoprotein complex. Highlights • The long noncoding RNA Blnc1 is conserved between mice and humans. • Human Blnc1 stimulates thermogenic gene expression during brown adipocyte differentiation. • hnRNPU physically interacts with human and mouse Blnc1. • hnRNPU promotes the assembly and function of the Blnc1/EBF2 ribonucleoprotein complex. |
| Databáze: | OpenAIRE |
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