Conservation of expression and alternative splicing in the prosaposin gene
Conservation of expression and alternative splicing in the prosaposin gene
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DOI：
10.1016/j.molbrainres.2004.06.027
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发表时间：
2004-10-22
期刊：
影响因子：
--
通讯作者：
Horowitz, M
中科院分区：
文献类型：
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作者：
Cohen, T;Ravid, L;Horowitz, M
皂苷是四种溶酶体激活剂分子的前体，即皂苷A、B、C和d。它也被分泌，并被认为是一种神经营养因子。神经营养功能归因于皂苷c的氨基端。在人类中，小鼠和大鼠的皂苷被转录成两种主要的同工异构体，在皂苷B结构域的第8外显子中包含9个bps。在本研究中，我们发现鸡和斑马鱼的丙苷结构和选择性剪接也存在进化保守性。此外，免疫组化检测显示，在小鼠和鸡发育中的大脑中，丙皂苷的表达有一定的保守性。我们开发了一种灵敏的测定方法来定量丙苷的选择性剪接形式。我们的研究结果表明，在小鼠脑、骨骼肌和心肌中，含有外显子8的RNA最丰富，而在内脏和平滑肌器官中几乎不存在。我们在小鼠和鸡的大脑以及发育过程中观察到交替剪接的丙皂苷mrna的时间和差异表达。在小鼠和鸡的大脑发育过程中，含有8号外显子的prosaposin RNA丰度的升高可能表明含有8号外显子的prosaposin形式在这一过程中起作用。(C) 2004 Elsevier B.V.版权所有
Prosaposin is the precursor of four lysosomal activator molecules known as saposins A, B, C and D. It is also secreted and was proposed to be a neurotrophic factor. The neurotrophic function was attributed to the amino terminus of saposin C. In man, mouse and rat prosaposin is transcribed to two major isoforms differing in the inclusion of 9 bps of exon 8 within the saposin B domain. In the present study, we show that there is evolutionary conservation of the prosaposin structure and alternative splicing in chick and zebrafish as well. Moreover, there is conservation in prosaposin expression as tested immunohistochemically in the mouse and chick developing brain. We developed a sensitive assay to quantitate the prosaposin alternatively spliced forms. Our results indicate that, in mouse brain, skeletal and cardiac muscle the exon 8-containing RNA is most abundant, while it is almost absent from visceral and smooth muscle-containing organs. We observed temporal and differential expression of the alternatively spliced prosaposin mRNAs in mouse and chick brain as well as during development. The elevation in the abundance of exon 8-containing prosaposin RNA during mouse and chick brain development may suggest a role for the exon 8-containing prosaposin form in this process. (C) 2004 Elsevier B.V. All rights reserved.