The Rps23rg gene family originated through retroposition of the ribosomal protein s23 mRNA and encodes proteins that decrease Alzheimer's β-amyloid level and tau phosphorylation
The Rps23rg gene family originated through retroposition of the ribosomal protein s23 mRNA and encodes proteins that decrease Alzheimer's β-amyloid level and tau phosphorylation
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DOI：
10.1093/hmg/ddq302
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发表时间：
2010-10-01
影响因子：
3.5
通讯作者：
Zhang, Yun-wu
中科院分区：
文献类型：
--
作者：
Huang, Xiumei;Chen, Yaomin;Zhang, Yun-wu
逆转录是基因起源的重要机制。然而，通过逆转录产生的新基因的功能，特别是与疾病相关的功能的研究是有限的。我们最近发现了一个小鼠基因，Rps 23 retroposed gene 1（Rps 23 rg 1），它调节β-淀粉样蛋白（A β）水平和tau蛋白磷酸化，这是阿尔茨海默病（AD）的两个主要病理标志，并发现Rps 23 rg 1起源于小鼠核糖体蛋白S23（Rps 23）mRNA的逆转录。在这里，我们表明，Rps 23 mRNA的逆转录发生多次在不同的物种，但只产生另一个功能性表达的Rps 23 rg 1同源基因，Rps 23 rg 2，在小鼠中，而人类可能没有功能性Rps 23 rg同源物。Rps 23 rg 1和Rps 23 rg 2都相对于亲本Rps 23基因转录，在各种组织中表达，并编码与腺苷酸环化酶相互作用的蛋白质。与RPS 23 RG 1蛋白类似，RPS 23 RG 2可以上调蛋白激酶A活性以降低糖原合成酶激酶-3的活性、A β水平和tau磷酸化。然而，RPS 23 RG 2的作用弱于RPS 23 RG 1的作用，这种差异可能归因于RPS 23 RG 2的额外羧基末端区域，该区域可能具有抑制作用。此外，我们表明，RPS 23 RG 1的跨膜结构域是其功能的重要。总之，我们的研究结果提出了一个新的基因家族，其产物和相关的信号通路可能会阻止小鼠发生AD样病变。
Retroposition is an important mechanism for gene origination. However, studies to elucidate the functions of new genes originated through retroposition, especially the functions related to diseases, are limited. We recently identified a mouse gene, Rps23 retroposed gene 1 (Rps23rg1), that regulates beta-amyloid (A beta) level and tau phosphorylation, two major pathological hallmarks of Alzheimer's disease (AD), and found that Rps23rg1 originated through retroposition of the mouse ribosomal protein S23 (Rps23) mRNA. Here we show that retroposition of Rps23 mRNA occurred multiple times in different species but only generated another functionally expressed Rps23rg1-homologous gene, Rps23rg2, in mice, whereas humans may not possess functional Rps23rg homologs. Both Rps23rg1 and Rps23rg2 are reversely transcribed relative to the parental Rps23 gene, expressed in various tissues and encode proteins that interact with adenylate cyclases. Similar to the RPS23RG1 protein, RPS23RG2 can upregulate protein kinase A activity to reduce the activity of glycogen synthase kinase-3, A beta level and tau phosphorylation. However, the effects of RPS23RG2 are weaker than those of RPS23RG1 and such a difference could be attributed to the extra carboxyl-terminal region of RPS23RG2, which may have an inhibitory effect. In addition, we show that the transmembrane domain of RPS23RG1 is important for its function. Together, our results present a new gene family, whose products and associated signaling pathways might prevent mice from developing AD-like pathologies.