AU-rich element

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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]

AREs are defined as a region with frequent adenine and uridine bases in a mRNA. They usually target the mRNA for degradation.[2][3] ARE-directed mRNA degradation is influenced by many exogenous factors, including phorbol esters, calcium ionophores, cytokines, and transcription inhibitors.[4] These observations suggest that AREs play a critical role in the regulation of gene transcription during cell growth and differentiation, and the immune response.[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 calledELAVL4) 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]

References[edit]

  1. ^ Chen, Chyi-Ying A.; Shyu, Ann-Bin (November 1995). "AU-rich elements: characterization and importance in mRNA degradation". Trends In Biochemical Science 20 (11): 465–470. doi:10.1016/S0968-0004(00)89102-1. PMID 8578590. 
  2. ^ C Barreau, L Paillard and H B Osborne (2006). "AU-rich elements and associated factors: are there unifying principles?". Nucleic Acids Res 33 (22): 7138–7150. doi:10.1093/nar/gki1012. PMC 1325018. PMID 16391004. 
  3. ^ Shaw G, Kamen R (August 1986). "A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation". Cell 46 (5): 659–67. doi:10.1016/0092-8674(86)90341-7. PMID 3488815. 
  4. ^ Chen, Chyi-Ying A.; Shyu, Ann-Bin (November 1995). "AU-rich elements: characterization and importance in mRNA degradation". Trends In Biochemical Science 20 (11): 465–470. doi:10.1016/S0968-0004(00)89102-1. PMID 8578590. 
  5. ^ Chen, Chyi-Ying A.; Shyu, Ann-Bin (November 1995). "AU-rich elements: characterization and importance in mRNA degradation". Trends In Biochemical Science 20 (11): 465–470. doi:10.1016/S0968-0004(00)89102-1. PMID 8578590. 
  6. ^ Federico Bolognani and Nora Perrone-Bizzozero (2008). "RNA-protein interactions and control of mRNA stability in neurons". J Neurosci Res 86 (3): 481–489. doi:10.1002/jnr.21473. PMID 17853436. 
  7. ^ Nora Perrone-Bizzozero and Federico Bolognani (2002). "Role of HuD and other RNA-binding proteins in neural development and plasticity". J Neurosci Res 68 (2): 121–126. doi:10.1002/jnr.10175. PMID 11948657. 
  8. ^ Gruber AR, Fallmann J, Kratochvill F, Kovarik P, Hofacker IL (2011). "AREsite: a database for the comprehensive investigation of AU-rich elements". Nucleic Acids Res 39 (Database issue): D66–9. doi:10.1093/nar/gkq990. PMC 3013810. PMID 21071424. 

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