Istituto di Fisiologia Clinica     
Pitto L., Ripoli A., Cremisi F., Simili M., Rainaldi G. MicroRNA (interference) networks are embedded in the gene regulatory networks. In: Cell Cycle, vol. 7 (16) pp. 2458 - 2461. Landes Bioscience, 2008.
MicroRNAs (miRNAs) are a class of endogenous 22-25 nt single-stranded RNA molecules that regulate gene expression post-transcriptionally. They are highly conserved among species with distinct temporal and spatial patterns of expression, each of them potentially interacting with hundreds of messenger RNAs. Since miRNAs, like transcription factors (TFs), are trans-acting factors that interact with cis-regulatory elements, they potentially generate a complex combinatorial code. Moreover, as TFs and genes containing binding sites for TFs have a high probability of being targeted by miRNAs, the basic interplay miRNA/TF renders miRNAs key components of gene regulatory networks. Several biological processes, including diseases such as cancer, have been causatively associated to disturbances of miRNAs/TF interplay both in vitro and in vivo. These aspects, cumulatively, indicate that miRNAs and transcription factors have a crucial role in determining cellular behaviour, highlighting the role of small RNA molecules in regulatory mechanisms and indicating other routes in the evolutionary path of gene expression. Transcription factors (TFs) are important components of gene regulatory networks.5 Like TFs, miRNAs are trans-acting factors that interact with many cis-regulatory elements. Therefore it is not surprising that they generate a complex combinatorial code.6 Recent data demonstrate that genes with many TF binding sites have a higher probability to be controlled by miRNAs than genes with few TF binding sites.7 In addition, the expression of genes co-transcribed with miRNAs (embedded miRNA genes) and that of the genes predicted to be targeted by such miRNAs, tends to be either positively or negatively correlated.8 Two classes of miRNA-TF circuitries have been identified: The first devoted to the maintenance of cellular homeostasis, the second dedicated to reinforce transcriptionally driven signalling.8 Emerging evidences indicating a crucial miRNA/TF interplay in many biological process (cell differentiation) and diseases (cancer) support the importance of miRNAs as key components of the gene regulatory network. Here we examine some examples of different types of miRNA/TF interaction so far described in the literature
URL: http://www.landesbioscience.com/journals/cc/article/6455
Subject microRNAs
transcription factors
mouse embryo fibroblasts
LRF downregulation

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