近年來，誘導(dǎo)多能干細胞（iPS）的引發(fā)了生命科學(xué)與醫(yī)學(xué)界干細胞研究的熱潮,。干細胞廣泛應(yīng)用的前提是明確其自我更新和定向分化的調(diào)控機制,。OCT4是參與調(diào)控胚胎干細胞自我更新和維持其全能性的最為重要的轉(zhuǎn)錄因子之一，同時也是體外建立誘導(dǎo)多能干細胞（iPS）的關(guān)鍵基因,。中國科學(xué)院遺傳發(fā)育所戴建武實驗室從事再生醫(yī)學(xué)研究,近年來在功能生物材料和干細胞研究中取得了一系列的創(chuàng)新成果,。
最近，戴建武實驗室在OCT4基因通過mRNA的選擇性拼接形成OCT4A和OCT4B兩種mRNA的基礎(chǔ)上,，首次發(fā)現(xiàn)了OCT4B mRNA存在選擇性起始翻譯現(xiàn)象,，以兩個AUG和一個CUG作為起始密碼子翻譯表達出OCT4B-265、OCT4B-190和OCT4B-164三種不同的蛋白異構(gòu),。確認了其mRNA上存在內(nèi)部核糖體插入位點（IRES）進行選擇性起始翻譯的調(diào)控,。并發(fā)現(xiàn)該IRES調(diào)控元件在應(yīng)激條件下的活性相對增強，由IRES調(diào)控翻譯的內(nèi)源OCT4B-190蛋白在應(yīng)激條件下表達上調(diào)，過表達OCT4B-190蛋白能夠增強細胞在應(yīng)激條件下抵抗凋亡的能力,。
這項研究表明OCT4基因在干細胞的增殖,、分化、應(yīng)激反應(yīng),、凋亡過程等多個生物學(xué)過程中發(fā)揮著重要的作用,。該研究對于了解OCT4基因蛋白質(zhì)種類的多樣性及功能的復(fù)雜性具有重要的參考價值。作為國家中長期重大科研計劃“調(diào)控干細胞自我更新的分子網(wǎng)絡(luò)研究”項目的首席科學(xué)家,，戴建武研究員表示“這項工作為研究干細胞自我更新分子網(wǎng)絡(luò)的調(diào)控開辟了新的途徑”,。該發(fā)現(xiàn)以該實驗室博士研究生王霞為第一作者發(fā)表在《干細胞》（Stem Cells） 上。 （生物谷Bioon.com）
生物谷推薦原始出處：
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.
