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The regulatory epicenter of miRNAs

IR@CSIR-IHBT

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Title The regulatory epicenter of miRNAs
 
Creator Jha, Gopaljee
Mehra, A
Shanker, R
 
Subject Plant sciences
 
Description 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.
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://ihbt.csircentral.net/1099/1/31.pdf
Jha, Gopaljee and Mehra, A and Shanker, R (2011) The regulatory epicenter of miRNAs. Journal of Biosciences, 36 (4). pp. 621-638.
 
Relation http://ihbt.csircentral.net/1099/