Abstract
BackgroundThe expression of microRNAs (miRNAs) is primarily regulated during their transcription. However, the transcriptional regulation of miRNA genes has not been studied extensively owing to the lack of sufficient information about the promoters and transcription start sites of most miRNAs.ResultsIn this study, we identified the transcription start sites of human primary miRNAs (pri-miRNAs) using DROSHA knockout cells. DROSHA knockout resulted in increased accumulation of pri-miRNAs and facilitated the precise mapping of their 5′ end nucleotides using the rapid amplification of cDNA ends (RACE) technique. By analyzing the promoter region encompassing the transcription start sites of miRNAs, we found that the unrelated miRNAs in their sequences have many common elements in their promoters for binding the same transcription factors. Moreover, by analyzing intronic miRNAs, we also obtained comprehensive evidence that miRNA-harboring introns are spliced more slowly than other introns.ConclusionsThe precisely mapped transcription start sites of pri-miRNAs, and the list of transcription factors for pri-miRNAs regulation, will be valuable resources for future studies to understand the regulatory network of miRNAs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3252-7) contains supplementary material, which is available to authorized users.
Highlights
The expression of microRNAs is primarily regulated during their transcription
From the analysis of the sequencing results, we confirmed that the number of reads from genomic regions encompassing miRNA hairpin sequences was highly increased in DROSHA knockout library compared to wild-type library (Fig. 1b and Additional file 2)
Compared to the sequencing reads obtained from the library made using wild-type cells, those from the DROSHA knockout library delineated the transcribed region more reliably (Fig. 1c and Additional file 3)
Summary
The expression of microRNAs (miRNAs) is primarily regulated during their transcription. The transcriptional regulation of miRNA genes has not been studied extensively owing to the lack of sufficient information about the promoters and transcription start sites of most miRNAs. Most of the biological pathways in cells are influenced by microRNAs (miRNAs) [1]. The precise regulation of miRNA expression is essential to maintain cellular homeostasis. Deviation from the wild-type expression of miRNAs results in diverse types of diseases [2, 3]. To fine-tune the expression of miRNAs, their maturation is regulated by multiple mechanisms. The regulatory steps in the miRNA biogenesis pathway include differential processing by nucleases such as DROSHA and DICER, nucleotide modification, and degradation at the intermediate step. MiRNA expression is primarily regulated through transcriptional control [1]
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