PURA, the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions.
PURA, the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions.
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DOI：
10.1016/j.gene.2017.12.004
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发表时间：
2018-02-15
期刊：
影响因子：
3.5
通讯作者：
Johnson EM
中科院分区：
文献类型：
--
作者：
Daniel DC;Johnson EM
PURA基因编码Pur-alpha，一种具有重复核酸结合结构域的322个氨基酸的蛋白质，其从细菌到人类高度保守。迄今为止，在螺旋体和拟杆菌中已经检测到具有该结构域的单拷贝的PUR基因。低等真核生物拥有一个PUR基因拷贝，而脊索动物拥有1-4个PUR家族成员。人PUR基因编码Pur-alpha（Pura）、Pur-beta（Purb）和两种形式的Pur-gamma（Purg）。Pur-alpha是一种结合特定DNA和RNA序列元件的蛋白质。人类PURA位于染色体带5 q31，受到三个启动子的复杂控制。PURA的整个蛋白质编码序列在单个外显子内是连续的。一些研究发现，Pura的过表达或显微注射抑制了致癌转化细胞的锚定非依赖性生长，并在G1-S或G2-M检查点阻断增殖。对细胞周期的影响可能是通过普拉与细胞蛋白质（包括Cyclin/Cdk复合物和Rb肿瘤抑制蛋白）的相互作用介导的。PURA基因敲除小鼠出生后不久死亡，影响大脑和造血发育。在人类中，环境诱导的PURA杂合缺失与骨髓增生异常综合征和急性髓细胞性白血病的进展有关。普拉通过与HIV-1蛋白达特结合在艾滋病中发挥作用。在脑中，神经胶质细胞中的达特和普拉联合激活JC多瘤病毒的转录和复制，JC多瘤病毒是引起脱髓鞘疾病、进行性多灶性白质脑病的因子。达特和普拉还可刺激HIV-1 RNA基因组的复制。在神经元中，普拉伴随mRNA转录到树突中的翻译位点。PURA基因座的微缺失与几种神经系统疾病有关。原发性PURA突变与一系列表型相关，提示潜在的PURA综合征。在几种脑部疾病中，核酸，富含G的Pura结合元件被扩增为扩展的多核苷酸重复序列，包括脆性X综合征和肌萎缩性侧索硬化症/额颞叶痴呆的家族性形式。在整个进化过程中，Pura蛋白基于其核酸结合特性的保守性在生存中起着关键作用。普拉的这些特性已经在高等生物体中适应了人类大脑的发展，而人类大脑的发展至今还无法估量。
The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1–4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements. Human PURA, located at chromosome band 5q31, is under complex control of three promoters. The entire protein coding sequence of PURA is contiguous within a single exon. Several studies have found that overexpression or microinjection of Pura inhibits anchorage-independent growth of oncogenically transformed cells and blocks proliferation at either G1-S or G2-M checkpoints. Effects on the cell cycle may be mediated by interaction of Pura with cellular proteins including Cyclin/Cdk complexes and the Rb tumor suppressor protein. PURA knockout mice die shortly after birth with effects on brain and hematopoietic development. In humans environmentally induced heterozygous deletions of PURA have been implicated in forms of myelodysplastic syndrome and progression to acute myelogenous leukemia. Pura plays a role in AIDS through association with the HIV-1 protein, Tat. In the brain Tat and Pura association in glial cells activates transcription and replication of JC polyomavirus, the agent causing the demyelination disease, progressive multifocal leukoencephalopathy. Tat and Pura also act to stimulate replication of the HIV-1 RNA genome. In neurons Pura accompanies mRNA transcripts to sites of translation in dendrites. Microdeletions in the PURA locus have been implicated in several neurological disorders. De novo PURA mutations have been related to a spectrum of phenotypes indicating a potential PURA syndrome. The nucleic acid, G-rich Pura binding element is amplified as expanded polynucleotide repeats in several brain diseases including fragile X syndrome and a familial form of amyotrophic lateral sclerosis/fronto-temporal dementia. Throughout evolution the Pura protein plays a critical role in survival, based on conservation of its nucleic acid binding properties. These Pura properties have been adapted in higher organisms to the as yet unfathomable development of the human brain.
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