Abstract
To identify the transcriptional promoters in the proximal regions of human microRNA (miRNA) genes, we analyzed the 5′ flanking regions of intergenic miRNAs and intronic miRNAs. With the TSSG program prediction, we found that the ratio of intronic-s miRNA genes with a least one promoter was significantly lower than those of intergenic miRNA genes and intronic-a miRNA genes. More than half of the miRNA genes have only one promoter and less than 20% of the miRNA genes have more than three promoters in the 5-kb upstream regions. All potential promoters are randomly distributed within these regions. Approximately 60% of the miRNA promoters have a TATA-like box, being significantly higher than that of all human promoters. Luciferase reporter assays showed that 22 of the 30 promoters drove gene expression in HEK-293 cells, indicating a high accuracy of the promoter prediction. This study lays a foundation for future investigation into the transcriptional regulatory mechanisms of human miRNA genes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Lee Y, Kim M, Han J et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060
Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (2004) Processing of primary microRNAs by the Microprocessor complex. Nature 432:231–235
Krutzfeldt J, Poy MN, Stoffel M (2006) Strategies to determine the biological function of microRNAs. Nat Genet 38 Suppl:S14–19
Bernstein E, Caudy AA, Hammond SM, Hannon GJ (2001) Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–366
Ambros V, Moss EG (1994) Heterochronic genes and the temporal control of C. elegans development. Trends Genet 10:123–127
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Carrington JC, Ambros V (2003) Role of microRNAs in plant and animal development. Science 301:336–338
Kloosterman WP, Plasterk RH (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450
Landgraf P, Rusu M, Sheridan R et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414
Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158
Saini HK, Griffiths-Jones S, Enright AJ (2007) Genomic analysis of human microRNA transcripts. Proc Natl Acad Sci USA 104:17719–17724
Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910
Ozsolak F, Poling LL, Wang Z et al (2008) Chromatin structure analyses identify miRNA promoters. Genes Dev 22:3172–3183
Marson A, Levine SS, Cole MF et al (2008) Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521–533
Hubbard TJ, Aken BL, Ayling S et al (2009) Ensembl 2009. Nucleic Acids Res 37:D690–D697
Solovyev V, Salamov A (1997) The Gene-Finder computer tools for analysis of human and model organisms genome sequences. Proc Int Conf Intell Syst Mol Biol 5:294–302
Altuvia Y, Landgraf P, Lithwick G et al (2005) Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 33:2697–2706
Gu J, He T, Pei Y et al (2006) Primary transcripts and expressions of mammal intergenic microRNAs detected by mapping ESTs to their flanking sequences. Mamm Genome 17:1033–1041
Liu R, States DJ (2002) Consensus promoter identification in the human genome utilizing expressed gene markers and gene modeling. Genome Res 12:462–469
Corcoran DL, Pandit KV, Gordon B, Bhattacharjee A, Kaminski N, Benos PV (2009) Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One 4:e5279
Zhou X, Ruan J, Wang G, Zhang W (2007) Characterization and identification of microRNA core promoters in four model species. PLoS Comput Biol 3:e37
Kim TH, Barrera LO, Zheng M et al (2005) A high-resolution map of active promoters in the human genome. Nature 436:876–880
Yang C, Bolotin E, Jiang T, Sladek FM, Martinez E (2007) Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene 389:52–65
Acknowledgments
We would like to thank an anonymous reviewer for her/his critical and constructive comments that led to the improvement of this paper. This work was supported by The National Natural Science Foundation of China (grant nos. 31070928, 30600198, 30870876 and 81000558) and The Guangzhou Scholar Program (grant nos. 10A011G and 10A012G). We are grateful to He Shanheng Charity Foundation for contributing to the development of this institute.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Long, YS., Deng, GF., Sun, XS. et al. Identification of the transcriptional promoters in the proximal regions of human microRNA genes. Mol Biol Rep 38, 4153–4157 (2011). https://doi.org/10.1007/s11033-010-0535-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-010-0535-y