MtiBase: a database for decoding microRNA target sites located within CDS and 5'UTR regions from CLIP-Seq and expression profile datasets

Abstract

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.

Figure 1.

Systematic overview of MtiBase core framework. The results generated by MtiBase are stored in a MySQL database and displayed on the web page.

Figure 2.

Sample output image for predicted miRNA target sites. MtiBase provides various options for users to optimize their search results. Additional information on the miRNA target sites could be obtained by clicking the ‘details’ button.

Figure 3.

Sample output image for miRNA function section. Apart from miRNA–target regulatory relationships, MtiBase also integrates the experimental data on the relationships to assess the effects of miRNAs on transcription and translation.