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Circuitry of mRNA regulation

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Abstract Some of the classical paradigms of gene regulation have been challenged by global‐scale analysis of eukaryotic transcriptional and post‐transcriptional gene regulation (PTGR), made possible by the development of genomics and proteomics tools. Post‐transcriptional events in particular are increasingly being recognized as important sources of gene regulation. The hundreds of regulatory RNA‐binding proteins that exist in eukaryotes may regulate dozens to hundreds of functionally related RNA targets. Likewise, the expression of considerable fractions of many eukaryotic genomes is affected by hundreds of non‐coding RNAs, e.g., microRNAs. These findings suggest an enormous regulatory potential for PTGR that may affect virtually every message in a cell. All gene regulatory systems are composed of simple network circuits that coordinate the transfer of regulatory signals to a target gene/message. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Biological Mechanisms > Regulatory Biology

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Basic network motifs in transcriptional and post‐transcriptional gene regulation. Each motif consists of one class of gene regulators, which may either activate or repress target gene expression. Note that miRNAs generally, but not always, act as repressors.42, 43 (A) Regulation of multiple messages by a single regulator. (B) Regulation of a single message by multiple regulators. (C) Autoregulation of gene regulators. (D) Multi‐component regulatory loop. (E) Feed‐forward loop.

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Selected composite gene regulatory network motifs. Proteins are represented by circles [RNA‐binding proteins (RBPs) in blue, transcription factors (TFs) in green], while miRNAs and target genes/mRNAs are depicted by orange and gray triangles, respectively. (A) Two‐component loop involving one RBP and one TF. (B) Two‐component loop involving one RBP and one miRNA. (C) Schematic representation of a hypothetical composite ‘regulon’. Each regulator binds and regulates the expression of different subsets of targets. Conversely, each target is bound by a distinct set of regulators in a combinatorial fashion.

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