Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR.

Brain-specific promoter and polyadenylation sites of the beta-adducin pre-mRNA generate an unusually long 3'-UTR.
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β-无元素前mRNA的脑特异性启动子和聚腺苷酸位点产生异常长的3'-UTR。

DOI:
10.1093/nar/gkj425
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发表时间:
2006
影响因子:
14.9
通讯作者:
Muro, AF
Muro, AF
中科院分区:
生物学2区
文献类型:
--
作者:
Costessi, L;Devescovi, G;Baralle, FE;Muro, AF

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Adducins是由α-,β-和γ-亚基组成的膜骨架蛋白家族,促进红细胞内肌动蛋白和血影蛋白的结合。α-和γ-亚基广泛表达,而β-亚基在脑和红细胞组织中广泛表达。脑内收蛋白的大小与脾相似,但β转录本是一种脑特有的转录本,目前尚未鉴定,估计长度为8-9kb,而不是脾mRNA3-4kb。在这里,我们通过确定大鼠、小鼠和人类大脑特异的β-内收蛋白转录本的结构,展示了这些差异的分子基础。我们在啮齿类动物中发现了一种大脑特异性启动子,显然在人类中没有保守。此外,我们提出的证据表明,脑-mRNAs是由一个共同的机制形成的,该机制包括组织特异性地使用替代的聚腺苷酸化位点产生长达6.6kb的异常长的3‘-非翻译区。这一假说得到了大脑特异性多聚腺苷酸化位点两侧高度保守区域的存在的支持,这些区域表明这些序列参与了β-Adducin转录本在大脑中的翻译调节、稳定性和/或亚细胞定位。
Adducins are a family of membrane skeleton proteins composed of α-, β- and γ-subunits that promote actin and spectrin association in erythrocytes. The α- and γ-subunits are expressed ubiquitously, while the β-subunit is found in brain and erythropoietic tissues. The brain β-adducin protein is similar in size to that of spleen, but the mRNA transcript is a brain-specific one that has not been yet characterized, having an estimated length of 8–9 kb instead of the 3–4 kb of spleen mRNA. Here, we show the molecular basis for these differences by determining the structure of the brain-specific β-adducin transcript in rats, mice and humans. We identified a brain-specific promoter in rodents that, apparently, was not conserved in humans. In addition, we present evidence that the brain-mRNAs are formed by a common mechanism consisting in the tissue-specific use of alternative polyadenylation sites generating unusually long 3′-untranslated region of up to 6.6 kb. This hypothesis is supported by the presence of highly-conserved regions flanking the brain-specific polyadenylation site that suggest the involvement of these sequences in the translational regulation, stability and/or subcellular localization of the β-adducin transcript in the brain.
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发表时间: 2005
影响因子: 14.9
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