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Isoform specific gene auto-regulation via miRNAs: a case study on miR-128b and ARPP-21 |
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| Authors: | Molly Megraw Praveen Sethupathy Kiranmai Gumireddy Shane T Jensen Qihong Huang Artemis G Hatzigeorgiou |
| Institution: | 1. Center for Bioinformatics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 2. Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 7. Institute for Genome Sciences and Policy, Duke University, Durham, NC, 27708, USA 8. Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA 5. The Wistar Institute, Philadelphia, PA, USA 3. Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA 4. Department of Computer and Information Science, School of Engineering, University of Pennsylvania, Philadelphia, PA, USA 6. Institute of Molecular Oncology, BSRC “Alexander Fleming”, Athens, Greece |
| Abstract: | In this study, we investigate whether miRNAs located within “host” protein-coding genes may regulate the expression of their host genes. We find that 43 of 174 miRNAs encoded within RefSeq genes are predicted to target their host genes. Statistical analysis of this phenomenon suggests that gene auto-regulation via miRNAs may be under positive selective pressure. Our analysis also indicates that several of the 43 miRNAs have a much lower expectation of targeting their host genes by chance than others. Among these examples, we identify miR-128b:ARPP-21 (cyclic AMP-regulated phosphoprotein, 21 kD) as a case in which both the miRNA and the target site are also evolutionarily conserved. We provide experimental support for this miRNA:target interaction via reporter silencing assays, and present evidence that this isoform-specific gene auto-regulation has been preserved in vertebrate species in order to prevent detrimental consequences of ARPP-21 over-expression in brain. |
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