関: ARE

WordNet

very productive; "rich seams of coal"
containing plenty of fat, or eggs, or sugar; "rich desserts"; "they kept gorging on rich foods"
having an abundant supply of desirable qualities or substances (especially natural resources); "blessed with a land rich in minerals"; "rich in ideas"; "rich with cultural interest"
high in mineral content; having a high proportion of fuel to air; "a rich vein of copper", "a rich gas mixture"
of great worth or quality; "a rich collection of antiques"
pleasantly full and mellow; "a rich tenor voice"
possessing material wealth; "her father is extremely rich"; "many fond hopes are pinned on rich uncles"
suggestive of or characterized by great expense; "a rich display"
a straight line that generates a cylinder or cone
one of four substances thought in ancient and medieval cosmology to constitute the physical universe; "the alchemists believed that there were four elements"
the situation in which you are happiest and most effective; "in your element"
the most favorable environment for a plant or animal; "water is the element of fishes"
the 1st letter of the Roman alphabet (同)a
the blood group whose red cells carry the A antigen (同)type_A, group A
violent or severe weather (viewed as caused by the action of the four elements); "they felt the full fury of the elements"

PrepTutorEJDIC

『金持ちの』,『富んだ』,豊かな / 《名詞的に》《the~;複数扱い》金持ちの人たち / (衣服・宝石・家具などが)高価でみごとな,ぜいたくな / (想像力などが)豊かな;(土地が)肥えた / (音・声が)豊かな,深みのある;(色が)濃い,あざやかな;(料理・酒の問が)濃くておいしい;(香りが)強い / 濃度が高い;(特に食物の)栄養価が高い,(油・卵・バターなどを多く含んで)濃厚な / 《話》非常におもしろい,こっけいな;《反晴的に》とんでもない,ばかげた
〈C〉(物質を構成する)元素 / 〈C〉《修飾語[句]を伴って》(…の)(基本的な)『要素』,『成分』;《しばしば複数形で》構成分子 / 〈C〉(生物に固有の)生息場所,環境;(人の)適所,本領 / 〈C〉《古》四大(しだい)[元素](自然界の基本的構成要素と考えられていた地(earth)・水(water)・風(air)・火(fire)の4大要素の一つ) / 《the elements》(雨・風・雪などの)自然力・風雨,(特に)悪天候 / 《the elements》(学問の)原理,初歩,概論
answer / ampere
『富』,財産,豊かさ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/15 21:16:06」(JST)

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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 rapid degradation.^[2]^[3]

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]

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 Urich 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.^[4] 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]

ARE Element 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.^[7]

Mechanism of ARE-Mediated Decay

AREs are recognized by RNA binding proteins such as tristetraprolin (TTP), AUF1, and Hu Antigen R (HuR).^[8] 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.^[8]

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

TTP’s expression is rapidly induced by insulin.^[9] Immunoprecipitation experiments have shown that TTP co-precipitates with an exosome, suggesting that it helps recruit exosomes to the mRNA containing AREs.^[10] 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.^[11] 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.^[12] 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:^[8]

The c-fos gene produces a transcription factor that is activated in several cancers, and it lacks the ARE elements.
c-myc gene, also responsible for producing transcription factors found in several cancers, has also been reported to lack the ARE elements.
The Cox-2 gene catalyses the production of prostaglandins—it overexpresses in several cancers, and is stabilized by the binding of CUGBP2 RNA-binding protein to ARE

References

^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Barreau, C (2005). "AU-rich Elements and Associated Factors: Are There Unifying Principles?". Nucleic Acids Research 33 (22): 7138–7150. PMID 1325018.
^ ^a ^b ^c Elliott, David; Ladomery, Michael (2011). Stability and Degradation of mRNA. Oxford: Oxford UP. p. 312.
^ Cao, H; JF Jr, Urban; RA, Anderson (Apr 2008). "Insulin Increases Tristetraprolin and Decreases VEGF Gene Expression in Mouse 3T3-L1 Adipocytes". Obesity 16 (6): 1208–1218.
^ Tiedje, Christopher; Kotlyarov, Alexey; Gaestel, Matthias (2010). "Molecular Mechanisms of Phosphorylation-regulated TTP (tristetraprolin) Action and Screening for Further TTP-interacting Proteins". Biochemical Society Transactions 38 (6): 1632–1637.
^ Dai, Weijun; Zhang, Gen; Makeyev, Eugene V. (24 Sep 2011). "RNA-binding Protein HuR Autoregulates Its Expression by Promoting Alternative Polyadenylation Site Usage". Nucleic Acids Research 40 (2): 787–800. doi:10.1093/nar/gkr783.
^ Brennan, C. M.; Steinz, J. A. (Feb 2001). "HuR and MRNA Stability". Cellular and Molecular Life Sciences CMLS 58 (2): 266–277.

External links

Original publication discovering AU-rich elements
mRNA Translational blockade by AU-rich elements
Brief introduction to mRNA regulatory elements
ARED: AU-rich element database
Transterm page for AU-Rich Element
AREsite: An online resource for the analysis of AREs

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