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MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gillen, Austin E. Gosalia, Nehal Leir, S. Harris, A. |
| Copyright Year | 2011 |
| Abstract | The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex temporal and spatial pattern of expression that is controlled by multiple cis-acting elements interacting with the basal promoter. Although significant progress has been made towards understanding these genomic elements, there have been no reports of post-transcriptional regulation of CFTR by miRNAs (microRNAs). In the present study, we identify two miRNAs, hsa-miR-145 and hsa-miR-494, which regulate CFTR expression by directly targeting discrete sites in the CFTR 3' UTR (untranslated region). We show that at least 12 miRNAs are capable of repressing endogenous CFTR mRNA expression in the Caco-2 cell line. Ten of these also inhibit expression of a reporter construct containing the CFTR 3' UTR in one or more cell lines, and five repress endogenous CFTR protein expression in Caco-2 cells. Moreover, at least three are expressed in primary human airway epithelial cells, where CFTR expression is maintained at low levels in comparison with intestinal cell lines. Three of the miRNAs that target CFTR, hsa-miR-384, hsa-miR-494 and hsa-miR-1246, also inhibit expression of a reporter carrying the Na(+)-K(+)-Cl(-) co-transporter SLC12A2 [solute carrier family 12 (Na(+)-K(+)-Cl(-) transporters), member 2] 3' UTR, suggesting that these miRNAs may play a more general role in regulating chloride transport in epithelial cells. |
| Starting Page | 25 |
| Ending Page | 32 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.biochemj.org/content/ppbiochemj/438/1/25.full.pdf |
| PubMed reference number | 21689072v1 |
| Alternate Webpage(s) | https://doi.org/10.1042/BJ20110672 |
| DOI | 10.1042/bj20110672 |
| Journal | The Biochemical journal |
| Volume Number | 438 |
| Issue Number | 1 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 3' Untranslated Regions Cultured Cell Line Cystic Fibrosis Transmembrane Conductance Regulator Leukemia, B-Cell Membrane Transport Proteins MicroRNAs SLC12A2 gene Sodium-Potassium-Chloride Symporters Solute Carrier Family Transcription, Genetic Transcriptional Regulation cellular targeting chloride transport protein expression |
| Content Type | Text |
| Resource Type | Article |
