Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs
Open Access
- 21 October 2014
- journal article
- Published by Cold Spring Harbor Laboratory in RNA
- Vol. 20 (12), 1878-1889
- https://doi.org/10.1261/rna.045633.114
Abstract
The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4+ T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1–encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.Keywords
Funding Information
- Introduction of Innovative R&D Team Program of Guangdong Province (2009010058)
- National Special Research Program for Important Infectious Diseases (2013ZX10001004)
- National Basic Research Program of China (2010CB912202)
- National Natural Science Foundation of China (30972620)
- Natural Science Foundation of Guangdong (9251008901000022)
- Research Fund for the Doctoral Program of Higher Education of China (20090171110083)
- National Natural Science Foundation of China (81301431)
- China Postdoctoral Science Foundation (2012M511866 and 2013T60824)
This publication has 70 references indexed in Scilit:
- A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic PlasticityCell, 2012
- Small RNA and transcriptional upregulationWIREs RNA, 2011
- The widespread regulation of microRNA biogenesis, function and decayNature Reviews Genetics, 2010
- Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcriptionNature, 2010
- Promoter-specific transcriptional interference and c-myc gene silencing by siRNAs in human cellsThe EMBO Journal, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- Antisense transcripts are targets for activating small RNAsNature Structural & Molecular Biology, 2008
- The RNA polymerase II core promoter — the gateway to transcriptionCurrent Opinion in Cell Biology, 2008
- Small dsRNAs induce transcriptional activation in human cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- c-Myc-regulated microRNAs modulate E2F1 expressionNature, 2005