Parkin transcript variants in rat and human brain
Parkin transcript variants in rat and human brain
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DOI：
10.1023/b:nere.0000035807.25370.5e
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Cavallaro, S
中科院分区：
文献类型：
--
作者：
D'Agata, V;Cavallaro, S
选择性剪接在扩大蛋白质多样性方面具有重要作用。我们已经确定了互补的DNA物种从成年大鼠和胎儿人脑编码7个新的剪接变异体的parkin，基因突变的常染色体隐性遗传青少年帕金森综合征（ARJP）。选择性剪接影响几乎所有以前表征的外显子，加上3个新的外显子72，156和180个核苷酸。这创造了表达数百种不同同种型的潜力。编码的parkin亚型具有不同的氨基酸组成、翻译后修饰和编码区。阳离子，以及最重要的分子结构。他们分歧的存在或不存在的泛素样结构域，一个或两个C3HC4环指，环指（IBR）结构域之间，和巯基蛋白酶活性位点，这还没有以前的特点。不同的表达模式发生在神经元和神经胶质细胞的原代培养物中。广泛剪接parkin产生的区域和结构的多样性，并可能有重要的影响，发病机制的基础ARJP。
Alternative splicing has an important role in expanding protein diversity. We have identified complementary DNA species from adult rat and fetal human brain encoding seven new splice variants of parkin, a gene mutated in autosomal recessive juvenile parkinsonism (ARJP). Alternative splicing affects almost all previously characterized exons, plus 3 new exons of 72, 156, and 180 nucleotides. This creates the potential to express hundreds of different isoforms. The encoded parkin isoforms have different amino acid composition, post-translational modi. cations, and, most important, molecular architectures. They diverge for the presence or absence of the ubiquitin-like domain, one or two C3HC4 ring fingers, the in-between ring fingers (IBR) domain, and a thiol proteases active site, which has not been previously characterized. Distinct expression patterns occur in primary cultures of neuronal and glial cells. Extensive splicing of parkin produces regional and structural diversity and may have important implications for the pathogenetic mechanisms underlying ARJP.