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Long Noncoding RNA MEG3-4 Tissue Specifically Modulates IL-1b by Competing Its Binding to Microrna-138 in Pulmonary Bacterial Infection
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A5484 - Long Noncoding RNA MEG3-4 Tissue Specifically Modulates IL-1b by Competing Its Binding to Microrna-138 in Pulmonary Bacterial Infection
Author Block: M. Wu; Biomedical Sciences, University of North Dakota, Grand Forks, ND, United States.
Long noncoding RNA MEG3-4 tissue specifically modulates IL-1β by competing its binding to microRNA-138 in pulmonary bacterial infection
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota.
Long noncoding RNAs (lncRNAs) are important regulators of gene expression; however, their functions in inflammatory responses to infection remain elusive. Here, we identify lncRNA MEG3 as a tissue specific modulator of inflammatory responses during bacterial infection. Among the 10 transcript isoforms of MEG3, transcript 4 is the most downregulated isoform in mouse lungs. Through a microRNA-138 complementary 3' region, MEG3-4 binds miR-138 as a competing endogenous RNA to release the miRNA’s target IL-1β mRNA, thereby intensifying inflammatory responses. Hence, we extend the decoy modulation mechanism for lncRNAs to anti-bacterial immunity, impacting phenotype and disease progression. MEG3-4 localizes in cytoplasm and regulates miR-138 levels to control IL-1β transcription, resulting in a balanced inflammatory response through feedback to NF-κB. Thus a critical timely down-regulation of MEG3-4 in vivo strongly inhibits proinflammatory responses, alleviating the progression of sepsis. Collectively, these findings reveal that MEG3-4 dynamically modulates pulmonary inflammatory responses through transcriptional regulation of immune response genes.
This project was supported by NIH R01 and INBRE grants, respectively.
Author Block: M. Wu; Biomedical Sciences, University of North Dakota, Grand Forks, ND, United States.
Long noncoding RNA MEG3-4 tissue specifically modulates IL-1β by competing its binding to microRNA-138 in pulmonary bacterial infection
Department of Biomedical Sciences, University of North Dakota, Grand Forks, North Dakota.
Long noncoding RNAs (lncRNAs) are important regulators of gene expression; however, their functions in inflammatory responses to infection remain elusive. Here, we identify lncRNA MEG3 as a tissue specific modulator of inflammatory responses during bacterial infection. Among the 10 transcript isoforms of MEG3, transcript 4 is the most downregulated isoform in mouse lungs. Through a microRNA-138 complementary 3' region, MEG3-4 binds miR-138 as a competing endogenous RNA to release the miRNA’s target IL-1β mRNA, thereby intensifying inflammatory responses. Hence, we extend the decoy modulation mechanism for lncRNAs to anti-bacterial immunity, impacting phenotype and disease progression. MEG3-4 localizes in cytoplasm and regulates miR-138 levels to control IL-1β transcription, resulting in a balanced inflammatory response through feedback to NF-κB. Thus a critical timely down-regulation of MEG3-4 in vivo strongly inhibits proinflammatory responses, alleviating the progression of sepsis. Collectively, these findings reveal that MEG3-4 dynamically modulates pulmonary inflammatory responses through transcriptional regulation of immune response genes.
This project was supported by NIH R01 and INBRE grants, respectively.
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