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Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

Croft, Larry, Szklarczyk, Damian, Jensen, Lars Juhl and Gorodkin, Jan 2012, Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs, BMC systems biology, vol. 6, no. 90, pp. 1-10, doi: 10.1186/1752-0509-6-90.

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Title Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs
Author(s) Croft, Larry
Szklarczyk, Damian
Jensen, Lars Juhl
Gorodkin, Jan
Journal name BMC systems biology
Volume number 6
Issue number 90
Start page 1
End page 10
Total pages 10
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2012-07-23
ISSN 1752-0509
Keyword(s) 3' Untranslated Regions
Animals
Computational Biology
Data Mining
Humans
Mice
MicroRNAs
Signal Transduction
Transcription Factors
Summary BACKGROUND: Transcription factors (TFs) have long been known to be principally activators of transcription in eukaryotes and prokaryotes. The growing awareness of the ubiquity of microRNAs (miRNAs) as suppressive regulators in eukaryotes, suggests the possibility of a mutual, preferential, self-regulatory connectivity between miRNAs and TFs. Here we investigate the connectivity from TFs and miRNAs to other genes and each other using text mining, TF promoter binding site and 6 different miRNA binding site prediction methods.

RESULTS: In the first approach text mining of PubMed abstracts reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3'UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes. Furthermore, a random sample of 986 TarBase entries was scored for experimental evidence by manual inspection of the original papers, and enrichment for TFs was observed to increase with score. Low-scoring TarBase entries, where experimental evidence is anticorrelated miRNA:mRNA expression with predicted miRNA targets, appear not to select for real miRNA targets to any degree. Our manually validated text-mining results also suggests that miRNAs may be activated by more TFs than other classes of genes, as 7% of miRNA:TF co-occurrences in the literature were TFs activating miRNAs. This was confirmed when thirdly, we found enrichment for predicted, conserved TF binding sites in miRNA and TF genes compared to other gene classes.

CONCLUSIONS: We see enrichment of connections between miRNAs and TFs using several independent methods, suggestive of a network of mutual activating and suppressive regulation. We have also built regulatory networks (containing 2- and 3-loop motifs) for mouse and human using predicted miRNA and TF binding sites and we have developed a web server to search and display these loops, available for the community at http://rth.dk/resources/tfmirloop.
Language eng
DOI 10.1186/1752-0509-6-90
Field of Research 1199 Other Medical And Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2012, Croft et al
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30106043

Document type: Journal Article
Collections: School of Life and Environmental Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.