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新型 OCT4 拼接变体 OCT4B1 可以通过 OCT4B 的拼接产生三种蛋白异构体。

The novel OCT4 spliced variant OCT4B1 can generate three protein isoforms by alternative splicing into OCT4B.

机构信息

Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.

出版信息

J Genet Genomics. 2010 Jul;37(7):461-5. doi: 10.1016/S1673-8527(09)60065-5.

DOI:10.1016/S1673-8527(09)60065-5
PMID:20659710
Abstract

OCT4 is one of the key transcription factors in maintaining the pluripotency and self-renewal of embryonic stem (ES) cells. Human OCT4 can generate two isoforms OCT4A and OCT4B by alternative splicing. OCT4B1 is a recently discovered novel OCT4 spliced variant, which has been considered as a putative marker of stemness. Compared with the OCT4B mRNA, OCT4B1 mRNA is generated by retaining intron 2 as a cryptic exon which contains a TGA stop codon in it. As a result, the protein product of OCT4B1 mRNA could be truncated. Interestingly, we present here that OCT4B1 can indirectly produce the same protein products as OCT4B. We have demonstrated that OCT4B1 mRNA can be spliced into OCT4B mRNA, and encode three protein isoforms. The splicing of OCT4B1 mRNA into OCT4B mRNA can be remarkably inhibited by the mutation of the classical splicing site. Our result suggests that OCT4B mRNA may originate from OCT4B1 mRNA by alternative splicing.

摘要

OCT4 是维持胚胎干细胞(ES 细胞)多能性和自我更新的关键转录因子之一。人类 OCT4 可以通过选择性剪接生成两种异构体 OCT4A 和 OCT4B。OCT4B1 是最近发现的一种新型 OCT4 剪接变异体,被认为是干性的潜在标志物。与 OCT4B mRNA 相比,OCT4B1 mRNA 通过保留内含子 2 作为隐藏外显子而产生,其中包含一个 TGA 终止密码子。因此,OCT4B1 mRNA 的蛋白产物可能会被截断。有趣的是,我们在此提出 OCT4B1 可以间接地产生与 OCT4B 相同的蛋白产物。我们已经证明,OCT4B1 mRNA 可以剪接成 OCT4B mRNA,并编码三种蛋白异构体。经典剪接位点的突变可显著抑制 OCT4B1 mRNA 剪接成 OCT4B mRNA。我们的结果表明,OCT4B mRNA 可能通过选择性剪接来源于 OCT4B1 mRNA。

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