Adenylate-uridylate-rich elements (AU-rich elements; AREs) are found in the 3' untranslated region (UTR) of many messenger RNAs (mRNAs) that code for proto-oncogenes, nuclear transcription factors, and cytokines. AREs are one of the most common determinants of RNA stability in mammalian cells.[1] The function of AREs was originally discovered by Shaw and Kamen in 1986.[2]
AREs are defined as a region with frequent adenine and uridine bases in a mRNA. They usually target the mRNA for rapid degradation.[3][2] ARE-directed mRNA degradation is influenced by many exogenous factors, including phorbol esters, calcium ionophores, cytokines, and transcription inhibitors. These observations suggest that AREs play a critical role in the regulation of gene transcription during cell growth and differentiation, and the immune response.[1] As evidence of its critical role, deletion of the AREs from the 3'UTR in either the TNF gene or GM-CSF gene in mice leads to over expression of each respective gene product, causing dramatic disease phenotypes.[4][5]
AREs have been divided into three classes with different sequences. The best characterised adenylate uridylate (AU)-rich Elements have a core sequence of AUUUA within U-rich sequences (for example WWWU(AUUUA)UUUW where W is A or U). This lies within a 50–150 base sequence, repeats of the core AUUUA element are often required for function.
A number of different proteins (e.g. HuA, HuB, HuC, HuD, HuR) bind to these elements and stabilise the mRNA while others (AUF1, TTP, BRF1, TIA-1, TIAR, and KSRP) destabilise the mRNA, miRNAs may also bind to some of them.[6] HuD (also called ELAVL4) binds to AREs and increases the half-life of ARE-bearing mRNAs in neurons during brain development and plasticity.[7]
AREsite—a database for ARE containing genes—has recently been developed with the aim to provide detailed bioinformatic characterization of AU-rich elements.[8]
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