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通过内部核糖体进入位点对OCT4进行的可变翻译及其在应激反应中的新功能。

Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response.

作者信息

Wang Xia, Zhao Yannan, Xiao Zhifeng, Chen Bing, Wei Zhanliang, Wang Bin, Zhang Jing, Han Jin, Gao Yuan, Li Lingsong, Zhao Hongxi, Zhao Wenxue, Lin Hang, Dai Jianwu

机构信息

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

出版信息

Stem Cells. 2009 Jun;27(6):1265-75. doi: 10.1002/stem.58.

DOI:10.1002/stem.58
PMID:19489092
Abstract

OCT4 is a pivotal transcription factor in maintaining the pluripotency and self-renewal capacities of embryonic stem (ES) cells. Human OCT4 can generate two isoforms by alternative splicing, termed OCT4A and OCT4B. OCT4A confers the stemness properties of ES cells, whereas the function of OCT4B is unknown. We present here the diverse protein products and a novel function of OCT4 gene. A single OCT4B mRNA can encode three isoforms by alternative translation initiation at AUG and CUG start codons, respectively. A putative internal ribosome entry site (IRES) has been identified in OCT4B mRNA accounting for the translation mechanism. The OCT4B-190 is upregulated under stress conditions and it may protect cell against apoptosis under stress. This work evokes the significance to distinguish the biological function of the protein products of OCT4. The OCT4 gene, by the regulation of alternative splicing and alternative translation initiation, may carry out more crucial roles in many biological events.

摘要

OCT4是维持胚胎干细胞(ES细胞)多能性和自我更新能力的关键转录因子。人类OCT4可通过可变剪接产生两种异构体,称为OCT4A和OCT4B。OCT4A赋予ES细胞干性特性,而OCT4B的功能尚不清楚。我们在此展示了OCT4基因多样的蛋白质产物和一种新功能。单个OCT4B mRNA可分别通过在AUG和CUG起始密码子处的可变翻译起始编码三种异构体。在OCT4B mRNA中已鉴定出一个假定的内部核糖体进入位点(IRES),这解释了其翻译机制。OCT4B - 190在应激条件下上调,它可能在应激状态下保护细胞免受凋亡。这项工作引发了区分OCT4蛋白质产物生物学功能的重要性。OCT4基因通过可变剪接和可变翻译起始的调控,可能在许多生物学事件中发挥更关键的作用。

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