The regulatory epicenter of miRNAs

Abstract

miRNAs are small non-coding RNAs with average length of ~21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and around the genomic sequences of precursor miRNAs and RNA-binding protein (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive manner. Here, we report that miRNA precursor regions are positionally enriched for binding of transcription factors as well as RBPs around the 3' end of mature miRNA region in 5' arm. The pattern and distribution of such regulatory sites appears to be a characteristic of precursor miRNA sequences when compared with non-miRNA sequences as negative dataset and tested statistically.When compared with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the enriched zone near the mature miRNA region. An expression-data-based correlation analysis was performed between such miRNAs and their corresponding transcription factors and RBPs for this region. Some specific groups of binding factors and associated miRNAs were identified. We also identified some of the overrepresented transcription factors and associated miRNAs with high expression correlation values which could be useful in cancer-related studies. The highly correlated groups were found to host experimentally validated composite regulatory modules, in which Lmo2-GATA1 appeared as the predominant one. For many of RBP-miRNAs associations, coexpression similarity was also evident among the associated miRNA common to given RBPs, supporting the Regulon model, suggesting a common role and common control of these miRNAs by the associated RBPs. Based on our findings, we propose that the observed characteristic distribution of regulatory sites in precursor miRNA sequence regions could be critical inmiRNA transcription, processing, stability and formation and are important for therapeutic studies. Our findings also support the recently proposed theory of self-sufficient mode of transcription by miRNAs, which states that miRNA transcription can be carried out in host-independent mode too.

Risk factors and biomarkers of age-related macular degeneration

“…Drosha is comprised of two RNase II domains. Of these, one is believed to cleave the 3′ end of the pre-miRNA while the 5′ end is cleaved by the other domain (Jha et al, 2011). Hairpin release occurs in the nucleus, and then the miRNA is exported to cytoplasm.…”

miR-BAG: Bagging Based Identification of MicroRNA Precursors

“…Therefore, due to its functional importance, the structure of miRNA containing region might be more conserved than the rest of the precursor regions. Also, some recent studies have suggested that this region harbors binding sites for factors critical for miRNA biogenesis [44], [45]. Though it is just a single feature among the array of various features considered in this study, structural profile matrices introduced in this study emerged as one of the most discriminating features.…”

miReader: Discovering Novel miRNAs in Species without Sequenced Genome

“…A few recent works have reported binding sites for transcription factors and RNA binding proteins in the mature miRNA region of precursors. Presence of such sites might be causing regulation of miRNA transcription as well as post-transcriptional fates of miRNAs [23]–[27]. Such functionally important regions are usually conserved.…”