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Transcription factor binding sites are highly enriched within microRNA precursor sequences

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posted on 15.08.2012 by Jittima Piriyapongsa, I King Jordan, Andrew B Conley, Tom Ronan, Neil R. Smalheiser
Background: Transcription factors are thought to regulate the transcription of microRNA genes in a manner similar to that of protein-coding genes; that is, by binding to conventional transcription factor binding site DNA sequences located in or near promoter regions that lie upstream of the microRNA genes. However, in the course of analyzing the genomics of human microRNA genes, we noticed that annotated transcription factor binding sites commonly lie within 70- to 110-nt long microRNA small hairpin precursor sequences. Results: We report that about 45% of all human small hairpin microRNA (pre-miR) sequences contain at least one predicted transcription factor binding site motif that is conserved across human, mouse and rat, and this rises to over 75% if one excludes primate-specific pre-miRs. The association is robust and has extremely strong statistical significance; it affects both intergenic and intronic pre-miRs and both isolated and clustered microRNA genes. We also confirmed and extended this finding using a separate analysis that examined all human pre-miR sequences regardless of conservation across species. Conclusions: The transcription factor binding sites localized within small hairpin microRNA precursor sequences may possibly regulate their transcription. Transcription factors may also possibly bind directly to nascent primary microRNA gene transcripts or small hairpin microRNA precursors and regulate their processing. Reviewers: This article was reviewed by Guillaume Bourque (nominated by Jerzy Jurka), Dmitri Pervouchine (nominated by Mikhail Gelfand), and Yuriy Gusev. Keywords: Transcription factors, microRNA biogenesis, drosha




Supported by the Stanley Medical Research Institute. JP is supported by the new researcher grant from the Thailand Research Fund and National Center for Genetic Engineering and Biotechnology. IKJ was supported by an Alfred P Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839).


Publisher Statement

© 2011 Piriyapongsa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DOI:10.1186/1745-6150-6-61


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