User:Hsse27/sandbox

Source: Wikipedia, the free encyclopedia.

ARE Elements

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 degradation.[2][3]

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

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

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. [6]


Mechanism of ARE-mediated decay

AREs are recognized by RNA binding proteins such as

ELAVL4) binds to AREs and increases the half-life of ARE-bearing mRNAs in neurons during brain development and plasticity.[9] Although the exact mechanism is not very well understood, recent publications have attempted to propose the action of some of these proteins. AUF1, also known as hnRNP D, binds AREs through RNA recognition motifs (RRMs). AUF1 is also known to interact with the translation initiation factor eIF4G and with poly(A)-binding protein, indicating that AUF1 senses the translational status of mRNA and decays accordingly through the excision of the poly(A) tail.[10]

Mechanism of ARE-Mediated mRNA Decay. Destabilizing RNA Binding proteins recruit exosomes to the RNA molecule while stabilizing proteins prevent such recruitment.

TTP’s expression is rapidly induced by insulin[11]. Immunoprecipitation experiments have shown that TTP co-precipitates with an exosome, suggesting that it helps recruit exosomes to the mRNA containing AREs [12]. Alternatively, HuR proteins have a stabilizing effect—their binding to AREs increases the half-life of mRNAs. Similar to other RNA-binding proteins, this class of proteins contain three RRMs, two of which are specific to ARE elements [13]. A likely mechanism for HuR action relies on the idea that these proteins compete with other proteins that normally have a destabilizing effect on mRNAs[14]. HuRs are involved in genotoxic response—they accumulate in the cytoplasm in response to UV exposure and stabilize mRNAs that encode proteins involved in DNA repair.

ARE Elements and 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 [15]:

AREsite - a database for ARE containing genes - has recently been developed with the aim to provide detailed bioinformatic characterization of AU-rich elements.[16]

References

  1. PMID 8578590
    .
  2. PMID 16391004
    .
  3. PMID 3488815
    .
  4. PMID 8578590
    .
  5. PMID 8578590
    .
  6. ^ Barreau, C. "AU-rich Elements and Associated Factors: Are There Unifying Principles? "Nucleic Acids Research (2005): 7138-150. Web. 11 Oct. 2014.
  7. ^ Elliott, David, and Michael Ladomery. "Stability and Degradation of MRNA." Molecular Biology of RNA. Oxford: Oxford UP, 2011. 312. Print
  8. PMID 17853436
    .
  9. PMID 11948657
    .
  10. ^ Elliott, David, and Michael Ladomery. "Stability and Degradation of MRNA." Molecular Biology of RNA. Oxford: Oxford UP, 2011. 312. Print
  11. ^ Cao, H., JF JR Urban, and RA Anderson. "Insulin Increases Tristetraprolin and Decreases VEGF Gene Expression in Mouse 3T3-L1 Adipocytes." National Center for Biotechnology Information. U.S. National Library of Medicine, 1 June 2008. Web. 11 Oct. 2014.
  12. ^ Tiedje, A., C. Kotlyarov, and M. Gaestel. "Molecular Mechanisms of Phosphorylation-regulated TTP (tristetraprolin) Action and Screening for Further TTP-interacting Proteins."National Center for Biotechnology Information. U.S. National Library of Medicine, 1 Dec. 2010. Web. 11 Oct. 2014
  13. ^ Dai, Weijun, Gen Zhang, and Eugene Makeyev. "RNA-binding Protein HuR Autoregulates Its Expression by Promoting Alternative Polyadenylation Site Usage." National Center for Biotechnology Information. U.S. National Library of Medicine, 24 Sept. 2011. Web. 11 Oct. 2014.
  14. ^ Brennan, CM, and JA Steitz. "HuR and MRNA Stability." National Center for Biotechnology Information. U.S. National Library of Medicine, 1 Feb. 2001. Web. 11 Oct. 2014
  15. ^ Elliott, David, and Michael Ladomery. "Stability and Degradation of MRNA." Molecular Biology of RNA. Oxford: Oxford UP, 2011. 313. Print
  16. PMID 21071424.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )

External links


Category:RNA Category:Gene expression Category:Cis-regulatory RNA elements

Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Hsse27/sandbox&oldid=632423497"