Alu-directed transcriptional regulation of some novel miRNAs
- Equal contributors
1 National Laboratory of Biomacromolecules, Center for Computing and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, PR China
2 Bioinformatics Research Group, Institute of Computing Technology, Chinese Academy of Sciences, No 6 Kexueyuan South Road, Zhongguancun Haidian District, Beijing 100190, PR China
3 Graduate School of the Chinese Academy of Science, 19A Yuquan Road, Beijing 100080, PR China
BMC Genomics 2009, 10:563 doi:10.1186/1471-2164-10-563Published: 30 November 2009
Despite many studies on the biogenesis, molecular structure and biological functions of microRNAs, little is known about the transcriptional regulatory mechanisms controlling the spatiotemporal expression pattern of human miRNA gene loci. Several lines of experimental results have indicated that both polymerase II (Pol-II) and polymerase III (Pol-III) may be involved in transcribing miRNAs. Here, we assessed the genomic evidence for Alu-directed transcriptional regulation of some novel miRNA genes in humans. Our data demonstrate that the expression of these Alu-related miRNAs may be modulated by Pol-III.
We present a comprehensive exploration of the Alu-directed transcriptional regulation of some new miRNAs. Using a new computational approach, a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST). We systematically demonstrated that 73 miRNAs including five known ones may be transcribed by Pol-III through Alu or MIR. Among the new miRNAs, 33 were determined by high-throughput Solexa sequencing. Real-time TaqMan PCR and Northern blotting verified that three newly identified miRNAs could be induced to co-express with their upstream Alu transcripts by heat shock or cycloheximide.
Through genomic analysis, Solexa sequencing and experimental validation, we have identified candidate sequences for Alu-related miRNAs, and have found that the transcription of these miRNAs could be governed by Pol-III. Thus, this study may elucidate the mechanisms by which the expression of a class of small RNAs may be regulated by their upstream repeat elements.