Post-transcriptional regulators in inflammation: exploring new avenues in biological therapeutics.
The biosynthesis of inflammatory mediators relies on controlling the biogenesis and utilization of their corresponding messenger RNAs (mRNAs). These latter "utilization steps" encompass post-transcriptional mechanisms that gradually and variably impose a series of flexible-rate limiting controls to modify the abundance of an mRNA and the rate of its translation to protein in response to environmental signals. Mechanistically, post-transcriptional machines comprise networks of RNA binding proteins (RBPs), which recognize, passively or inducibly, secondary or tertiary ribonucleotide structures located on their target RNAs. The outcome of these interactions is the stringent control of mRNA maturation, localization, turnover and translation. It is conceivable that if these post-transcriptional interactions fail, they may perturb cellular re-sponses to provide the impetus for chronic disease. Such is the case of the signal-responsive mechanisms affecting inflammatory mRNAs containing the AU-rich family of elements (AREs), which are recognized by a specific subset of RBPs. Intense research in this area has yielded important insight on the specific signals and mechanisms affecting the utilization of ARE-containing mRNAs. Here, we indicate briefly the inflammatory relevance of ARE-related mechanisms to highlight their importance in pathophysiology and their potential in the development of future biological therapies.
Katsanou
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BSRC Alexander Fleming, Institute of Immunology, 34 A1. Fleming Str, 16672 Vari, Greece.
Dimitriou
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M
Kontoyiannis
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DL
D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics*; D039102:Poly(A)-Binding Proteins / Q000502:physiology; D016601:RNA-Binding Proteins / Q000502:physiology; D000074019:T-Cell Intracellular Antigen-1; D051816:Tristetraprolin / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics