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Identification of novel Taz isoforms and functional comparison in pluripotency maintenance of mouse embryonic stem cells
Gene ( IF 2.6 ) Pub Date : 2020-12-29 , DOI: 10.1016/j.gene.2020.145383
Yixiao Xu , Lianlian Liu , Xueyue Wang , Yuyan Huang , Yuda Cheng , Junlei Zhang , Jiali Wang , Yanping Tian , Jiaxiang Xiong , Yi Yang , Bangqi Ren , Wei Wu , Ping He , Yue Zhang , Binyu Zhao , Jiaqi Wang , Meng Yu , Jiangjun Wang , Rui Jian , Yong Liu , Yan Ruan

Alternative splicing (AS) is a key process to expand the diversity of mRNA and protein from the genome and it is crucial for fate determination of embryonic stem cells (ESCs) by encoding isoforms with different functions to regulate the balance between pluripotency maintenance and differentiation. Since the role of the Hippo pathway in ESCs is controversial, there may be novel isoforms of Taz, a key effector of the Hippo pathway, previously unknown to us. Here, we identified three variants of Taz in mESCs. Apart from the canonical Taz1185, there were also two novel variants, Taz402 and Taz1086. We found their structure and subcellular localization to be different, while they could all interact with TEAD2 with similar binding affinities and activate transcription. Under the LIFlow condition, overexpression of them all induced apoptosis and differentiation of mESCs, among which the phenotype of Taz1086 was the most dramatic. Taken together, we discovered novel variants of Taz and compared their structure and functional differences in mESC pluripotency maintenance. These findings will help us to understand the Taz gene and clarify its role in mESC.



中文翻译:

新型Taz亚型的鉴定和小鼠胚胎干细胞多能性维持的功能比较

选择性剪接(AS)是扩大基因组中mRNA和蛋白质多样性的关键过程,对于通过编码具有不同功能的同工型来调节多能性维持和分化之间的平衡,对于决定胚胎干细胞(ESC)的命运至关重要。由于Hippo途径在ESC中的作用是有争议的,因此可能存在Taz的新型同工型,Taz是Hippo途径的关键效应子,以前我们并不知道。在这里,我们确定了mESC中Taz的三个变体。除了规范的Taz1185外,还有两个新颖的变体Taz402和Taz1086。我们发现它们的结构和亚细胞定位是不同的,尽管它们都可以与TEAD2具有相似的结合亲和力相互作用并激活转录。在LIF低下在这些条件下,它们的过度表达都诱导了mESCs的凋亡和分化,其中Taz1086的表型最为明显。总之,我们发现了Taz的新型变体,并比较了它们在mESC多能性维持中的结构和功能差异。这些发现将有助于我们了解Taz基因并阐明其在mESC中的作用。

更新日期:2020-12-29
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