The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.
The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.
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DOI：
10.1186/1471-2164-5-97
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发表时间：
2004-12-21
期刊：
影响因子：
4.4
通讯作者：
Bhak J
中科院分区：
文献类型：
--
作者：
An HJ;Lee D;Lee KH;Bhak J
哺乳动物mRNA序列的显著部分（约8%）在其3'非翻译区（UTR）含有富含Au（腺嘌呤和尿嘧啶）的元件或战神。这些mRNA序列通常是稳定的。然而，越来越多的观察已经作出了不稳定的物种，可能取决于某些元素，如铝重复。ARE基序是四聚体AUUU的重复序列和在重复序列末端的单体A（（AUUU）nA）。战神在生物学中的重要性在于它们使某些mRNA不稳定。原癌基因，如人类的c-fos、c-myc和c-jun，与战神相关。虽然已经知道ARE基序数量的增加导致含有ARE重复序列的mRNA的半衰期减少，但确切的机制尚不清楚。我们分析了战神和Alu的出现，并提出了一个可能的机制，人类mRNA如何获得和保持战神在其3' UTR起源于Alu重复。Alu重复序列散布在人类基因组中，占mRNA序列3' UTR的5%。Alu在其末端具有聚腺嘌呤（poly-A）区域，其导致在其互补Alu的末端的聚胸腺嘧啶（poly-T）区域。已经发现战神存在于poly-T区域。从NCBI的参考mRNA序列数据库的3' UTR，我们发现近40%（38.5%）的ARE（I类）在ARE序列中的一个错配允许内与Alu序列相关（表1）。其他ARE类也有统计学意义的关联。鉴于其数量有限，这远非随机发生。在每个ARE类别中，随机分布被模拟1,000次，并且显示ARE模式和Alu重复之间存在特殊关系。定义的是类。（本研究中使用符号标记，而非完整序列。）战神是影响mRNA在3'非翻译区的稳定或降解的介导序列元件。然而，战神的机制和起源是未知的。我们报告说，Alu是ARE的来源。我们发现，最长的战神的一半来自互补的Alu的多聚T区域。
A significant portion (about 8% in the human genome) of mammalian mRNA sequences contains AU (Adenine and Uracil) rich elements or AREs at their 3' untranslated regions (UTR). These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUU)nA). The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A) regions at its end, which lead to poly-thymine (poly-T) regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5%) of ARE (Class I) were associated with Alu sequences (Table 1) within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. Defined ARE classes. (Symbol marks are used in this study instead of full sequences.) AREs are mediating sequence elements affecting the stabilization or degradation of mRNA at the 3' untranslated regions. However, AREs' mechanism and origins are unknown. We report that Alu is a source of ARE. We found that half of the longest AREs were derived from the poly-T regions of the complementary Alu.
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DOI：
10.1084/jem.173.2.349
发表时间：
1991-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Peppel K;Vinci JM;Baglioni C
通讯作者：
Baglioni C
DOI：
10.1073/pnas.91.13.6148
发表时间：
1994-06-21
影响因子：
11.1
作者：
BRITTEN, RJ
通讯作者：
BRITTEN, RJ
影响因子：
5.3
作者：
CHEN, CYA;CHEN, TM;SHYU, AB
通讯作者：
SHYU, AB
影响因子：
5.3
作者：
BREWER, G
通讯作者：
BREWER, G
影响因子：
11.4
作者：
Anderson, JSJ;Parker, R
通讯作者：
Parker, R