Abstract
MicroRNAs are a class of important post-transcriptional regulators. Genetic and somatic mutations in miRNAs, especially those in the seed regions, have profound and broad impacts on gene expression and physiological and pathological processes. Over 500 SNPs were mapped to the miRNA seeds, which are located at position 2–8 of the mature miRNA sequences. We found that the central positions of the miRNA seeds contain fewer genetic variants and therefore are more evolutionary conserved than the peripheral positions in the seeds. We developed a knowledge-based method to analyse the functional impacts of mutations in miRNA seed regions. We computed the gene ontology-based similarity score GOSS and the GOSS percentile score for all 517 SNPs in miRNA seeds. In addition to the annotation of SNPs for their functional effects, in the present article we also present a detailed analysis pipeline for finding the key functional changes for seed SNPs. We performed a detailed gene ontology graph-based analysis of enriched functional categories for miRNA target gene sets. In the analysis of a SNP in the seed region of hsa-miR-96 we found that two key biological processes for progressive hearing loss ‘Neurotrophin TRK receptor signaling pathway’ and ‘Epidermal growth factor receptor signaling pathway’ were significantly and differentially enriched by the two sets of allele-specific target genes of miRNA hsa-miR-96.
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Acknowledgements
The authors gratefully acknowledge the editorial assistance of Dr Martha M. Howe provided through the Writing Assistance Program of the College of Graduate Health Sciences. This work was partly supported by The University of Tennessee Center for Integrative and Translational Genomics.
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[Bhattacharya A and Cui Y 2015 Knowledge-based analysis of functional impacts of mutations in microRNA seed regions. J. Biosci.] DOI 10.1007/s12038-015-9560-2
Supplementary materials pertaining to this article are available on the Journal of Biosciences Website at http://www.ias.ac.in/jbiosci/oct2015/supp/Bhattacharya.pdf
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Bhattacharya, A., Cui, Y. Knowledge-based analysis of functional impacts of mutations in microRNA seed regions. J Biosci 40, 791–798 (2015). https://doi.org/10.1007/s12038-015-9560-2
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DOI: https://doi.org/10.1007/s12038-015-9560-2