Guo Zhi-Wei, Xie Chen, Yang Jian-Rong, Li Jun-Hao, Yang Jian-Hua, Zheng Limin
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol.
Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Database (Oxford). 2015;2015. doi: 10.1093/database/bav102.
MicroRNAs (miRNAs) play an important role in the regulation of gene expression. Previous studies on miRNA functions mainly focused on their target sites in the 3' untranslated regions (UTRs) of mRNAs. However, increasing evidence has revealed that miRNAs can also induce mRNA degradation and mediate translational repression via complementary interactions with the coding sequence (CDS) and 5'UTR of mRNAs. In this study, we developed a novel database, MtiBase, to facilitate the comprehensive exploration of CDS- and 5'UTR-located miRNA target sites identified from cross-linking immunoprecipitation sequencing (CLIP-Seq) datasets and to uncover their regulatory effects on mRNA stability and translation from expression profile datasets. By integrating 61 Argonaute protein-binding CLIP-Seq datasets and miRNA target sites predicted by five commonly used programs, we identified approximately 4 400 000 CDS-located and 470 000 5'UTR-located miRNA target sites. Moreover, we evaluated the regulatory effects of miRNAs on mRNA stability and translation using the data from 222 gene expression profiles, and 28 ribosome-protected fragment sequencing, and six pulsed stable isotope labeling with amino acids in culture. Finally, the effects of SNPs on the functions of miRNA target sites were systematically evaluated. Our study provides a useful tool for functional studies of miRNAs in regulating physiology and pathology. Database URL: http://mtibase.sysu.edu.cn.
微小RNA(miRNA)在基因表达调控中发挥着重要作用。以往关于miRNA功能的研究主要集中在其在mRNA的3'非翻译区(UTR)中的靶位点。然而,越来越多的证据表明,miRNA也可以通过与mRNA的编码序列(CDS)和5'UTR的互补相互作用诱导mRNA降解并介导翻译抑制。在本研究中,我们开发了一个新的数据库MtiBase,以促进对从交联免疫沉淀测序(CLIP-Seq)数据集中鉴定出的位于CDS和5'UTR的miRNA靶位点进行全面探索,并从表达谱数据集中揭示它们对mRNA稳定性和翻译的调控作用。通过整合61个AGO蛋白结合CLIP-Seq数据集和五个常用程序预测的miRNA靶位点,我们鉴定出了约440万个位于CDS的和47万个位于5'UTR的miRNA靶位点。此外,我们使用来自222个基因表达谱、28个核糖体保护片段测序以及六个培养物中氨基酸脉冲稳定同位素标记的数据,评估了miRNA对mRNA稳定性和翻译的调控作用。最后,系统地评估了单核苷酸多态性(SNP)对miRNA靶位点功能的影响。我们的研究为miRNA在调节生理和病理过程中的功能研究提供了一个有用的工具。数据库网址:http://mtibase.sysu.edu.cn。