RNA polymerase III transcribes human microRNAs (original) (raw)

Nature Structural & Molecular Biology volume 13, pages 1097–1101 (2006)Cite this article

Abstract

Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.

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Acknowledgements

The authors are grateful to Robert Roeder at Rockefeller University for antibodies to Pol III, TFIIIB and TFIIIC subunits, for the BN51 cell line and for suggestions for the ChIP studies. We also thank S. Harper, R. Boudreau, C. Stein and S. Eliason for assistance and discussions, M. Welsh, R. Cornell and P. McCray for manuscript review and C. McLennan for manuscript assistance. This work was supported by the US National Institutes of Health (HD 44093; NS 50210) and the Roy J. Carver Trust.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Iowa, Iowa City, 52242, Iowa, USA
    Glen M Borchert & Beverly L Davidson
  2. Genetics Training Program, University of Iowa, Iowa City, 52242, Iowa, USA
    Glen M Borchert & William Lanier
  3. Department of Biological Sciences, University of Iowa, Iowa City, 52242, Iowa, USA
    William Lanier
  4. Department of Neurology, University of Iowa, Iowa City, 52242, Iowa, USA
    Beverly L Davidson
  5. Department of Physiology & Biophysics, University of Iowa, Iowa City, 52242, Iowa, USA
    Beverly L Davidson

Authors

  1. Glen M Borchert
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  2. William Lanier
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  3. Beverly L Davidson
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Contributions

G.M.B. conceived the study, collected the experimental data and contributed to the identification of repetitive element–microRNA associations, design and planning of the wet-lab experimentation, analysis of the experimental and computational findings and writing of the manuscript. W.L. contributed to the identification of repetitive element–microRNA associations and computational analysis. B.L.D. contributed to design and planning of the wet-lab experimentation, analysis of the experimental and computational findings and writing of the manuscript. All authors edited and approved the final version of the manuscript.

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Correspondence toBeverly L Davidson.

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The authors declare no competing financial interests.

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Borchert, G., Lanier, W. & Davidson, B. RNA polymerase III transcribes human microRNAs.Nat Struct Mol Biol 13, 1097–1101 (2006). https://doi.org/10.1038/nsmb1167

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