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miRNA regulatory circuits in ES cells differentiation: a chemical kinetics modeling approach.

Luo Z, Xu X, Gu P, Lonard D, Gunaratne PH, Cooney AJ, Azencott R - PLoS ONE (2011)

Bottom Line: For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data.When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction.This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, University of Houston, Houston, Texas, United States of America. boluomiduo1@gmail.com

ABSTRACT
MicroRNAs (miRNAs) play an important role in gene regulation for Embryonic Stem cells (ES cells), where they either down-regulate target mRNA genes by degradation or repress protein expression of these mRNA genes by inhibiting translation. Well known tables TargetScan and miRanda may predict quite long lists of potential miRNAs inhibitors for each mRNA gene, and one of our goals was to strongly narrow down the list of mRNA targets potentially repressed by a known large list of 400 miRNAs. Our paper focuses on algorithmic analysis of ES cells microarray data to reliably detect repressive interactions between miRNAs and mRNAs. We model, by chemical kinetics equations, the interaction architectures implementing the two basic silencing processes of miRNAs, namely "direct degradation" or "translation inhibition" of targeted mRNAs. For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data. When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction. This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation.

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Related in: MedlinePlus

A few key regulatory loops for ES cells according to [5].Arrows indicate “activation” while bars ending with a hash indicate “repression”.
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pone-0023263-g002: A few key regulatory loops for ES cells according to [5].Arrows indicate “activation” while bars ending with a hash indicate “repression”.

Mentions: To detect interacting miRNA-mRNA pairs [5], used qualitative correlation of expression profiles, mostly for miRMNA classes HL and LH, without any conclusions for miRNA class TR. For Wild Type ES cells differentiation [5], outlined a regulatory network (see Figure 2 [5]) involving the orphan nuclear receptor GCNF (NR6A1), which is a transcriptional repressor of Oct4 and Nanog. Both Oct4 protein and Nanog protein are transcriptional regulators for two groups of mRNAs: the Self-Renewal Regulators SRR (Sox2, Klf4, Esrrb, Tbx3, cMyc), and the Differentiation Inhibitors DI such as the Polycomb complex (Ezh1, Ezh2, Eed). In the Figure 2 network, the miRNAs of class HL target and the Hox cluster, while miRNAs of class LH target .


miRNA regulatory circuits in ES cells differentiation: a chemical kinetics modeling approach.

Luo Z, Xu X, Gu P, Lonard D, Gunaratne PH, Cooney AJ, Azencott R - PLoS ONE (2011)

A few key regulatory loops for ES cells according to [5].Arrows indicate “activation” while bars ending with a hash indicate “repression”.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198445&req=5

pone-0023263-g002: A few key regulatory loops for ES cells according to [5].Arrows indicate “activation” while bars ending with a hash indicate “repression”.
Mentions: To detect interacting miRNA-mRNA pairs [5], used qualitative correlation of expression profiles, mostly for miRMNA classes HL and LH, without any conclusions for miRNA class TR. For Wild Type ES cells differentiation [5], outlined a regulatory network (see Figure 2 [5]) involving the orphan nuclear receptor GCNF (NR6A1), which is a transcriptional repressor of Oct4 and Nanog. Both Oct4 protein and Nanog protein are transcriptional regulators for two groups of mRNAs: the Self-Renewal Regulators SRR (Sox2, Klf4, Esrrb, Tbx3, cMyc), and the Differentiation Inhibitors DI such as the Polycomb complex (Ezh1, Ezh2, Eed). In the Figure 2 network, the miRNAs of class HL target and the Hox cluster, while miRNAs of class LH target .

Bottom Line: For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data.When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction.This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, University of Houston, Houston, Texas, United States of America. boluomiduo1@gmail.com

ABSTRACT
MicroRNAs (miRNAs) play an important role in gene regulation for Embryonic Stem cells (ES cells), where they either down-regulate target mRNA genes by degradation or repress protein expression of these mRNA genes by inhibiting translation. Well known tables TargetScan and miRanda may predict quite long lists of potential miRNAs inhibitors for each mRNA gene, and one of our goals was to strongly narrow down the list of mRNA targets potentially repressed by a known large list of 400 miRNAs. Our paper focuses on algorithmic analysis of ES cells microarray data to reliably detect repressive interactions between miRNAs and mRNAs. We model, by chemical kinetics equations, the interaction architectures implementing the two basic silencing processes of miRNAs, namely "direct degradation" or "translation inhibition" of targeted mRNAs. For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data. When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction. This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation.

Show MeSH
Related in: MedlinePlus