近年来，诱导多能干细胞（iPS）的引发了生命科学与医学界干细胞研究的热潮。干细胞广泛应用的前提是明确其自我更新和定向分化的调控机制。OCT4是参与调控胚胎干细胞自我更新和维持其全能性的最为重要的转录因子之一，同时也是体外建立诱导多能干细胞（iPS）的关键基因。中国科学院遗传发育所戴建武实验室从事再生医学研究,近年来在功能生物材料和干细胞研究中取得了一系列的创新成果。
最近，戴建武实验室在OCT4基因通过mRNA的选择性拼接形成OCT4A和OCT4B两种mRNA的基础上，首次发现了OCT4B mRNA存在选择性起始翻译现象，以两个AUG和一个CUG作为起始密码子翻译表达出OCT4B-265、OCT4B-190和OCT4B-164三种不同的蛋白异构。确认了其mRNA上存在内部核糖体插入位点（IRES）进行选择性起始翻译的调控。并发现该IRES调控元件在应激条件下的活性相对增强，由IRES调控翻译的内源OCT4B-190蛋白在应激条件下表达上调，过表达OCT4B-190蛋白能够增强细胞在应激条件下抵抗凋亡的能力。
这项研究表明OCT4基因在干细胞的增殖、分化、应激反应、凋亡过程等多个生物学过程中发挥着重要的作用。该研究对于了解OCT4基因蛋白质种类的多样性及功能的复杂性具有重要的参考价值。作为国家中长期重大科研计划“调控干细胞自我更新的分子网络研究”项目的首席科学家，戴建武研究员表示“这项工作为研究干细胞自我更新分子网络的调控开辟了新的途径”。该发现以该实验室博士研究生王霞为第一作者发表在《干细胞》（Stem Cells） 上。 （生物谷Bioon.com）
生物谷推荐原始出处：
Stem Cells，doi: 10.1002/stem.58，Xia Wang ，Jianwu Dai
Alternative Translation of OCT4 by an Internal Ribosome Entry Site and its Novel Function in Stress Response
Xia Wang 1 2, Yannan Zhao 1, Zhifeng Xiao 1, Bing Chen 1, Zhanliang Wei 1, Bin Wang 1, Jing Zhang 1, Jin Han 1, Yuan Gao 1, Lingsong Li 3, Hongxi Zhao 3, Wenxue Zhao 1, Hang Lin 1, Jianwu Dai 1 *§
1Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China
2The Graduate School, Chinese Academy of Sciences, Beijing 100190, China
3Stem Cell Research Center, Peking University, Beijing 100083, China
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 embryonic stem 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 up-regulated 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.
