The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network
Open accessAbstract
microRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. It is anticipated that, in combination with transcription factors (TFs), they span a regulatory network that controls thousands of mammalian genes. Here we set out to uncover local and global architectural features of the mammalian miR regulatory network. Using evolutionarily conserved potential binding sites of miRs in human targets, and conserved binding sites of TFs in promoters, we uncovered two regulation networks. The first depicts combinatorial interactions between pairs of miRs with many shared targets. The network reveals several levels of hierarchy, whereby a few miRs interact with many other lowly connected miR partners. We revealed hundreds of "target hubs" genes, each potentially subject to massive regulation by dozens of miRs. Interestingly, many of these target hub genes are transcription regulators and they are often related to various developmental processes. The second network consists of miR-TF pairs that coregulate large sets of common targets. We discovered that the network consists of several recurring motifs. Most notably, in a significant fraction of the miR-TF coregulators the TF appears to regulate the miR, or to be regulated by the miR, forming a diversity of feed-forward loops. Together these findings provide new insights on the architecture of the combined transcriptional-post transcriptional regulatory network.
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Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs
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Structure and dynamics of molecular networks: A novel paradigm of drug discovery
Csermely, P., Korcsmáros, T., Kiss, H. J. M., London, G., & Nussinov, R. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.016 · Cited by 892
MicroRNA functions in stress responses
Leung, A. K. L., & Sharp, P. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.027 · Cited by 865
A network-biology perspective of microRNA function and dysfunction in cancer
Bracken, C. P., Scott, H. S., & Goodall, G. J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.134 · Cited by 668
The deep evolution of metazoan microRNAs
Wheeler, B. M., Heimberg, A. M., Moy, V. N., Sperling, E. A., Holstein, T. W., Heber, S., & Peterson, K. J. (2009) · Evolution & Development · doi:10.1111/j.1525-142x.2008.00302.x · Cited by 534
Non-coding RNA regulatory networks
Panni, S., Lovering, R. C., Porras, P., & Orchard, S. (2020) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2019.194417 · Cited by 479
Metadata
- Authors
- Shalgi, R., Lieber, D., Oren, M., & Pilpel, Y.
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-07-13
- Volume
- 3
- Issue
- 7
- Pages
- e131
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- OpenAlex
- W1980389572
- Cited by
- 512
- References
- 50
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- gold
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