Lai, Xin, Schmitz, Ulf, Gupta, Shailendra K., Bhattacharya, Animesh, Kunz, Manfred, Wolkenhauer, Olaf, and Vera, Julio (2012) Computational analysis of target hub gene repression regulated by multiple and cooperative miRNAs. Nucleic Acids Research, 40 (18). pp. 8818-8834.

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Abstract

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.

Item ID:	69017
Item Type:	Article (Research - C1)
ISSN:	1362-4962
Copyright Information:	© The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Date Deposited:	25 Jun 2024 03:47
FoR Codes:	31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310201 Bioinformatic methods development @ 33% 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310202 Biological network analysis @ 33% 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310114 Systems biology @ 34%
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