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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Computational analysis of target hub gene repression regulated by multiple and cooperative miRNAs
Nucleic Acids Research, Volume 40, No. 18, Year 2012
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Description
MicroRNA (miRNA) target hubs are genes that can be simultaneously targeted by a comparatively large number of miRNAs, a class of non-coding RNAs that mediate post-transcriptional gene repression. Although the details of target hub regulation remain poorly understood, recent experiments suggest that pairs of miRNAs can cooperate if their binding sites reside in close proximity. To test this and other hypotheses, we established a novel approach to investigate mechanisms of collective miRNA repression. The approach presented here combines miRNA target prediction and transcription factor prediction with data from the literature and databases to generate a regulatory map for a chosen target hub. We then show how a kinetic model can be derived from the regulatory map. To validate our approach, we present a case study for p21, one of the first experimentally proved miRNA target hubs. Our analysis indicates that distinctive expression patterns for miRNAs, some of which interact cooperatively, fine-tune the features of transient and long-term regulation of target genes. With respect to p21, our model successfully predicts its protein levels for nine different cellular functions. In addition, we find that high abundance of miRNAs, in combination with cooperativity, can enhance noise buffering for the transcription of target hubs. © 2012 The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3467055/bin/supp_40_18_8818__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3467055/bin/supp_gks657_nar-02874-a-2011-File014.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3467055/bin/supp_gks657_nar-02874-a-2011-File015.xls
Authors & Co-Authors
Lai, Xin
Germany, Rostock
Universität Rostock
Schmitz, Ulf
Germany, Rostock
Universität Rostock
Gupta, Shailendra Kumar
India, Lucknow
Indian Institute of Toxicology Research
Bhattacharya, Animesh
Germany, Leipzig
Universität Leipzig
Kunz, Manfred
Germany, Leipzig
Universität Leipzig
Wolkenhauer, Olaf
Germany, Rostock
Universität Rostock
South Africa, Stellenbosch
Stellenbosch University
Vera, Julio
Germany, Rostock
Universität Rostock
Statistics
Citations: 76
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1093/nar/gks657
ISSN:
03051048
e-ISSN:
13624962
Research Areas
Genetics And Genomics
Study Design
Case Study
Study Approach
Qualitative