標題: Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data
作者: Chien, Chia-Hung
Sun, Yi-Ming
Chang, Wen-Chi
Chiang-Hsieh, Pei-Yun
Lee, Tzong-Yi
Tsai, Wei-Chih
Horng, Jorng-Tzong
Tsou, Ann-Ping
Huang, Hsien-Da
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
公開日期: 1-十一月-2011
摘要: MicroRNAs (miRNAs) are critical small non-coding RNAs that regulate gene expression by hybridizing to the 3'-untranslated regions (3'-UTR) of target mRNAs, subsequently controlling diverse biological processes at post-transcriptional level. How miRNA genes are regulated receives considerable attention because it directly affects miRNA-mediated gene regulatory networks. Although numerous prediction models were developed for identifying miRNA promoters or transcriptional start sites (TSSs), most of them lack experimental validation and are inadequate to elucidate relationships between miRNA genes and transcription factors (TFs). Here, we integrate three experimental datasets, including cap analysis of gene expression (CAGE) tags, TSS Seq libraries and H3K4me3 chromatin signature derived from high-throughput sequencing analysis of gene initiation, to provide direct evidence of miRNA TSSs, thus establishing an experimental-based resource of human miRNA TSSs, named miRStart. Moreover, a machine-learning-based Support Vector Machine (SVM) model is developed to systematically identify representative TSSs for each miRNA gene. Finally, to demonstrate the effectiveness of the proposed resource, an important human intergenic miRNA, hsa-miR-122, is selected to experimentally validate putative TSS owing to its high expression in a normal liver. In conclusion, this work successfully identified 847 human miRNA TSSs (292 of them are clustered to 70 TSSs of miRNA clusters) based on the utilization of high-throughput sequencing data from TSS-relevant experiments, and establish a valuable resource for biologists in advanced research in miRNA-mediated regulatory networks.
URI: http://dx.doi.org/10.1093/nar/gkr604
http://hdl.handle.net/11536/14947
ISSN: 0305-1048
DOI: 10.1093/nar/gkr604
期刊: NUCLEIC ACIDS RESEARCH
Volume: 39
Issue: 21
起始頁: 9345
結束頁: 9356
顯示於類別:期刊論文


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  1. 000297375700032.pdf