These databases focus on interactions between miRNAs and lncRNAs, and identified interactions through a bioinformatics pipeline that integrating data from several in silico target prediction studies, Argonaute-CLIP datasets, and expression profiles.
In sum, our analyses of the CLIP datasets confirmed that many of the CLIP clusters and CLASH/chimera interactions lacking a seed match nonetheless capture authentic miRNA-binding sites otherwise the top enriched motifs would not pair so often to the cognate miRNA.
Applying this type of analysis to non-canonical interactions identified from miRNA mRNA chimeras in standard AGO CLIP datasets confirmed that these interactions are also enriched for pairing to the miRNA (Grosswendt et al., 2014).
Many miRNA mRNA chimeras can also be found in standard AGO CLIP datasets, presumably generated by an endogenous ligase acting in cell lysates during workup (Grosswendt et al., 2014).
To test this, we calculated the distances between SRSF1-4-binding clusters based on the previously published CLIP-seq datasets and the nearest mA sites.
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.
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 public expression quantitative trait locus (eQTL) data, miRNA binding site predictions, small RNA sequencing, and Argonaute crosslinking immunoprecipitation (AGO-CLIP) datasets, we identified genetic variants that can affect gene expression by modulating miRNA binding efficiency.
To identify the Ago-binding regions, 61 Ago CLIP-Seq (HITS-CLIP, PAR-CLIP and CLASH) datasets from human and mouse were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) (25) or starBase (13 , 26 (details in Supplementary materials).
Datasets and Code available.
By analysing the 61 Ago CLIP-Seq datasets, we identified ∼260 000 and 34 000 Ago-binding regions within the CDS and 5′UTR regions, respectively (Table 1).
