About miRNAs, miRNA seeds, target genes and target pathways
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Tim Kehl1,*, Christina Backes2,*, Fabian Kern2, Tobias Fehlmann2, Nicole Ludwig3, Eckart Meese3, Hans-Peter Lenhof1 and Andreas Keller2,*
1Center for Bioinformatics, Saarland University, Saarland Informatics Campus, Saarbrücken, Germany
2Chair for Clinical Bioinformatics, Saarland University, Saarland Informatics Campus, Saarbrücken, Germany
3Department of Human Genetics, Saarland University, Homburg, Germany
*These authors have contributed equally to this work
Andreas Keller, email: [email protected]
Keywords: non-coding RNA; systems biology; target gene; microRNA
Received: July 27, 2017 Accepted: September 21, 2017 Published: November 09, 2017
miRNAs are typically repressing gene expression by binding to the 3’ UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways.
By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade.
The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).
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