Expression analysis of an evolutionarily conserved alternative splicing factor, Sfrs10, in age-related macular degeneration.
Expression analysis of an evolutionarily conserved alternative splicing factor, Sfrs10, in age-related macular degeneration.
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DOI：
10.1371/journal.pone.0075964
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kanadia R
中科院分区：
文献类型：
--
作者：
Karunakaran DK;Banday AR;Wu Q;Kanadia R
老年性黄斑变性(AMD)是老年人群中最常见的致盲原因。在光感受器的微环境中产生的低氧应激被认为是导致AMD病理生理的根本原因。然而，AMD与选择性剪接介导的基因调控之间的联系还没有得到很好的研究。选择性剪接是人类的主要机制之一，通过这种机制，较少的蛋白质编码基因能够产生巨大的蛋白质组。在这里，我们研究了一个已知的应激反应基因和一种称为富含丝氨酸的剪接因子10(Sfrs10)的选择性剪接因子的表达。Sfrs10是富含丝氨酸-精氨酸(SR)的蛋白质家族中的一员，在大多数哺乳动物的氨基酸水平上是100%相同的。免疫印迹分析显示，小鼠、大鼠和鸡的视网膜提取物显示单一的免疫反应条带。此外，在成年小鼠、大鼠和鸡的视网膜上的免疫组织化学显示泛视网膜表达。然而，在正常人视网膜中没有检测到SFRS10，但在AMD视网膜中观察到明显的核斑点。这与之前的报告一致，该报告显示Sfrs10是一种应激反应基因，在低氧条件下上调。Sfrs10在人类和低等哺乳动物中表达的差异以及在AMD中SFRS10的上调进一步反映在这些物种之间启动子序列的差异上。最后，SFRS10+斑点与SC35+SR蛋白斑点或HSF1+应激颗粒无关。总之，我们的数据表明，SFRS10基因上调并形成明显的应激诱导斑点，可能参与了AMD应激反应基因的表达。
Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population. Hypoxic stress created in the micro-environment of the photoreceptors is thought to be the underlying cause that results in the pathophysiology of AMD. However, association of AMD with alternative splicing mediated gene regulation is not well explored. Alternative Splicing is one of the primary mechanisms in humans by which fewer protein coding genes are able to generate a vast proteome. Here, we investigated the expression of a known stress response gene and an alternative splicing factor called Serine-Arginine rich splicing factor 10 (Sfrs10). Sfrs10 is a member of the serine-arginine (SR) rich protein family and is 100% identical at the amino acid level in most mammals. Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and chicken retinae showed pan-retinal expression. However, SFRS10 was not detected in normal human retina but was observed as distinct nuclear speckles in AMD retinae. This is in agreement with previous reports that show Sfrs10 to be a stress response gene, which is upregulated under hypoxia. The difference in the expression of Sfrs10 between humans and lower mammals and the upregulation of SFRS10 in AMD is further reflected in the divergence of the promoter sequence between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR protein speckles or the HSF1+ stress granules. In all, our data suggests that SFRS10 is upregulated and forms distinct stress-induced speckles and might be involved in AS of stress response genes in AMD.
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影响因子：
4.1
作者：
BOULTON, M;MARSHALL, J
通讯作者：
MARSHALL, J
DOI：
10.1016/s0169-328x(98)00255-1
发表时间：
1998-11-20
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Kiryu-Seo, S;Matsuo, N;Kiyama, H
通讯作者：
Kiyama, H
鉴定进化保守的外显子是发育中剪接激活剂TRA2β的调节靶标。
影响因子：
4.5
作者：
Grellscheid S;Dalgliesh C;Storbeck M;Best A;Liu Y;Jakubik M;Mende Y;Ehrmann I;Curk T;Rossbach K;Bourgeois CF;Stévenin J;Grellscheid D;Jackson MS;Wirth B;Elliott DJ
通讯作者：
Elliott DJ
影响因子：
17.8
作者：
Curcio, Christine A.;Johnson, Mark;Huang, Jiahn-Dar;Rudolf, Martin
通讯作者：
Rudolf, Martin
DOI：
10.1002/ar.a.20336
发表时间：
2006-07-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Hall, Lisa L.;Smith, Kelly P.;Lawrence, Jeanne B.
通讯作者：
Lawrence, Jeanne B.