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Isoform specific gene auto-regulation via miRNAs: a case study on miR-128b and ARPP-21

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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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Acknowledgments

A.G.H., M.M., and P.S. were supported by an NSF Career Award (DBI-0238295). P.S. was also supported by a predoctoral NIH training grant (5T32GM008216). S.T.J. was supported by a University of Pennsylvania Research Foundation Grant. Q.H. and K.G. were supported by the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health, and Wistar startup fund.

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Author notes

  1. Molly Megraw

    Present address: Institute for Genome Sciences and Policy, Duke University, Durham, NC, 27708, USA

  2. Praveen Sethupathy

    Present address: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Center for Bioinformatics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Molly Megraw, Praveen Sethupathy & Artemis G. Hatzigeorgiou

  2. Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Molly Megraw, Praveen Sethupathy & Artemis G. Hatzigeorgiou

  3. Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA

    Shane T. Jensen

  4. Department of Computer and Information Science, School of Engineering, University of Pennsylvania, Philadelphia, PA, USA

    Artemis G. Hatzigeorgiou

  5. The Wistar Institute, Philadelphia, PA, USA

    Kiranmai Gumireddy & Qihong Huang

  6. Institute of Molecular Oncology, BSRC “Alexander Fleming”, Athens, Greece

    Artemis G. Hatzigeorgiou

Authors
  1. Molly Megraw
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  2. Praveen Sethupathy
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  3. Kiranmai Gumireddy
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  4. Shane T. Jensen
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  5. Qihong Huang
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  6. Artemis G. Hatzigeorgiou
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Corresponding authors

Correspondence to Qihong Huang or Artemis G. Hatzigeorgiou.

Additional information

Dedicated to Professor Sandor Suhai on the occasion of his 65th birthday and published as part of the Suhai Festschrift Issue.

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Megraw, M., Sethupathy, P., Gumireddy, K. et al. Isoform specific gene auto-regulation via miRNAs: a case study on miR-128b and ARPP-21. Theor Chem Acc 125, 593–598 (2010). https://doi.org/10.1007/s00214-009-0647-4

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  • DOI: https://doi.org/10.1007/s00214-009-0647-4

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