Identification of phylogenetically conserved microRNA cis-regulatory elements across 12 Drosophila species.
BACKGROUND
MicroRNAs are a class of endogenous small RNAs that play regulatory roles. Intergenic miRNAs are believed to be transcribed independently, but the transcriptional control of these crucial regulators is still poorly understood.


RESULTS
In this work, phylogenetic footprinting is used to identify conserved cis-regulatory elements (CCEs) surrounding intergenic miRNAs in Drosophila. With a two-step strategy that takes advantage of both alignment-based and motif-based methods, we identified CCEs that are conserved across the 12 fly species. When compared with TRANSFAC database, these CCEs are significantly enriched in known transcription factor binding sites (TFBSs). Moreover, several TFs that play essential roles in Drosophila development (e.g. Adf-1, Abd-B, Sd, Prd, Ubx, Zen and En) are found to be preferentially regulating the miRNA genes. Further analysis revealed many over-represented cis-regulatory modules (CRMs) composed of multiple known TFBSs, motif pairs with significant distance constraints and a number of novel motifs, many of which preferentially occur near the transcription start site of protein-coding genes. Additionally, a number of putative miRNA-TF regulatory feedback loops were also detected.


BACKGROUND
Supplementary Material and the Perl scripts performing two-step phylogenetic footprinting are available at http://bioinfo.au.tsinghua.edu.cn/member/xwwang/mircisreg
Wang
Xiaowo
X
MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.
Gu
Jin
J
Zhang
Michael Q
MQ
Li
Yanda
Y
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D004330:Drosophila / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D020537:RNA, Small Nucleolar / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D013045:Species Specificity
D035683:MicroRNAs; D020537:RNA, Small Nucleolar