AU-rich element

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Adenylate-uridylate-rich elements (AU-rich elements; AREs) are found in the

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

mRNA. They usually target the mRNA for rapid degradation.[2][3]

ARE-directed mRNA degradation is influenced by many exogenous factors, including

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]

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

HuD (also called ELAVL4) binds to AREs and increases the half-life of ARE-bearing mRNAs in neurons during brain development and plasticity.[5]

AREsite—a database for ARE containing genes—has recently been developed with the aim to provide detailed bioinformatic characterization of AU-rich elements.[6]

Classifications

  • Class I ARE elements, like the
    c-fos
    gene, have dispersed AUUUA motifs within or near U-rich regions.
  • Class II elements, like the
    GM-CSF
    gene, have overlapping AUUUA motifs within or near U-rich regions.
  • Class III elements, like the
    c-jun
    gene, are a much less well-defined class—they have a U-rich region but no AUUUA repeats.

No real ARE consensus sequence has been determined yet, and these categories are based neither on the same biological functions, nor on the homologous proteins.[2]

Mechanism of ARE-mediated decay

AREs are recognized by RNA binding proteins such as

AUF1 senses the translational status of mRNA and decays accordingly through the excision of the poly(A) tail.[7]

Proposed ARE Element Mechanism.
The proposed mechanism for which ARE elements function & control sequencing.

TTP's expression is rapidly induced by insulin.

mRNAs
that encode proteins involved in DNA repair.

Disease

Problems with

mRNA stability have been identified in viral genomes, cancer cells, and various diseases. Research shows that many of these problems arise because of faulty ARE function. Some of these problems have been listed below:[7]

References

  1. ^
    PMID 8578590
    .
  2. ^
    PMID 16391004
    .
  3. S2CID 40332253
    .
  4. S2CID 27076039
    .
  5. PMID 11948657
    .
  6. PMID 21071424
    .
  7. ^ a b c Elliott, David; Ladomery, Michael (2011). Stability and Degradation of mRNA. Oxford: Oxford UP. p. 312.
  8. S2CID 19149343
    .
  9. PMID 21118139
    .
  10. PMID 21948791
    .
  11. S2CID 35201269
    .

External links
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