Association of PAP-1 and Prp3p, the products of causative genes of dominant retinitis pigmentosa, in the tri-snRNP complex
Association of PAP-1 and Prp3p, the products of causative genes of dominant retinitis pigmentosa, in the tri-snRNP complex
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DOI：
10.1016/j.yexcr.2004.08.022
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发表时间：
2005-01-01
影响因子：
3.7
通讯作者：
Iguchi-Ariga, SMM
中科院分区：
文献类型：
--
作者：
Maita, H;Kitaura, H;Iguchi-Ariga, SMM
PAP-1是一种与Pim-1结合的蛋白质，最近被认为是常染色体显性视网膜色素变性（adRP）RP 9的缺陷基因。我们已经证明PAP-1在前体mRNA剪接中起作用。由于adRP的4个致病基因PAP-1、Prp 31、Prp 8和Prp 3编码的蛋白质具有剪接因子或剪接调节因子的功能，因此我们在本研究中研究了PAP-1与Prp 3 p和Prp 31 p的相互作用。结果表明，PAP-1与人细胞和酵母中的Prp 3 p相互作用，而与Prp 31 p不相互作用，PAP-1的碱性区和Prp 3 p的C端区是adRP突变点附近的结合区。此外，在Ba/F3和K562细胞中，通过蔗糖密度梯度分析，发现Prp 3 p和PAP-1的一部分是剪接体的一种形式U4/U6.U5-tri-snRNP复合物的组分，这表明PAP-1与剪接体弱相关。这些结果还表明，涉及adRP的剪接因子单独或相互有助于视网膜中的适当剪接，并且其功能的丧失导致adRP的发作。(C)2004年爱思唯尔公司All rights reserved.
PAP-1 has been identified by us as a Pim-1-binding protein and has recently been implicated as the defective gene in RP9, one type of autosomal dominant retinitis pigmentosa (adRP). We have then shown that PAP-1 plays a role in pre-mRNA splicing. Because four causative genes for adRP, including PAP-1, Prp31, Prp8, and Prp3, encode proteins that function as splicing factors or splicing-modulating factors, we investigated the interaction of PAP-1 with Prp3p and Prp31p in this study. The results showed that PAP-1 interacted with Prp3p but not Prp31p in human cells and yeast, and that the basic region of PAP-1 and the C-terminal region of Prp3p, regions beside spots found in adRP mutations, were needed for binding. Furthermore, both Prp3p and a part of PAP-1 were found to be components of the U4/U6.U5-tri-snRNP complex, one form of the spliceosome, in Ba/F3 and K562 cells by analysis of sucrose density gradients, suggesting that PAP-1 is weakly associated with the spliceosome. These results also suggest that splicing factors implicated in adRP contribute alone or mutually to proper splicing in the retina and that loss of their functions leads to onset of adRP. (C) 2004 Elsevier Inc. All rights reserved.