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PRMT1 Modulates Processing of Asthma-Related Primary MicroRNAs (Pri-miRNAs) into Mature miRNAs in Lung Epithelial Cells
- Source :
- The Journal of Immunology. 206:11-22
- Publication Year :
- 2021
- Publisher :
- The American Association of Immunologists, 2021.
-
Abstract
- Protein arginine methyltransferase-1 (PRMT1) is an important epigenetic regulator of cell function and contributes to inflammation and remodeling in asthma in a cell type–specific manner. Disease-specific expression patterns of microRNAs (miRNA) are associated with chronic inflammatory lung diseases, including asthma. The de novo synthesis of miRNA depends on the transcription of primary miRNA (pri-miRNA) transcript. This study assessed the role of PRMT1 on pri-miRNA to mature miRNA process in lung epithelial cells. Human airway epithelial cells, BEAS-2B, were transfected with the PRMT1 expression plasmid pcDNA3.1-PRMT1 for 48 h. Expression profiles of miRNA were determined by small RNA deep sequencing. Comparing these miRNAs with datasets of microarrays from five asthma patients (Gene Expression Omnibus dataset), 12 miRNAs were identified that related to PRMT1 overexpression and to asthma. The overexpression or knockdown of PRMT1 modulated the expression of the asthma-related miRNAs and their pri-miRNAs. Coimmunoprecipitation showed that PRMT1 formed a complex with STAT1 or RUNX1 and thus acted as a coactivator, stimulating the transcription of pri-miRNAs. Stimulation with TGF-β1 promoted the interaction of PRMT1 with STAT1 or RUNX1, thereby upregulating the transcription of two miRNAs: let-7i and miR-423. Subsequent chromatin immunoprecipitation assays revealed that the binding of the PRMT1/STAT1 or PRMT1/RUNX1 coactivators to primary let-7i (pri-let-7i) and primary miR (pri-miR) 423 promoter was critical for pri-let-7i and pri-miR-423 transcription. This study describes a novel role of PRMT1 as a coactivator for STAT1 or RUNX1, which is essential for the transcription of pri-let-7i and pri-miR-423 in epithelial cells and might be relevant to epithelium dysfunction in asthma.
- Subjects :
- Protein-Arginine N-Methyltransferases
Immunology
Respiratory Mucosa
Cell Line
Transforming Growth Factor beta1
Transcription (biology)
Coactivator
microRNA
Humans
Immunology and Allergy
Epigenetics
STAT1
RNA Processing, Post-Transcriptional
RNA, Small Interfering
Promoter Regions, Genetic
Lung
Gene knockdown
biology
Sequence Analysis, RNA
Gene Expression Profiling
Asthma
Cell biology
Repressor Proteins
Gene expression profiling
MicroRNAs
STAT1 Transcription Factor
Core Binding Factor Alpha 2 Subunit
biology.protein
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 206
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....c3f11674febfe0f2419dcb04289743f1