CURRENT POSITION AND ADDRESS

　　Title: Associate Professor, College of Veterinary Medicine, Northwest Agriculture and Forestry University, Shaanxi, China

　　Address: Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest Agriculture and Forestry University, Yangling District, Shaanxi 712100, China

　　Phone: 86-29-87080092

　　Email: liuxu1658@nwsuaf.edu.cn

　　EDUCATION BACKGROUND AND PROFESSIONAL EXPERIENCE

　　Associate Professor (2015-present)----College of Veterinary Medicine, Northwest A&F University, China

　　Postdoc (2014-2015)----College of Life Science, Northwest A&F University, China (Major: Development Biology, Advisor: Yong Zhang)

　　Ph.D. (2009-2014)-----College of Veterinary Medicine, Northwest A&F University, China (Major: Animal Embryonic Engineering, Mentor: Yong Zhang)

　　B.Sc. (2005-2009)----- College of Life Science, Northwest A&F University, China (Major: Biotechnology )

　　RESEARCH INTERESTS

　　My research interest focuses are: a. the physiological functions of alternative splicing (AS) in mammalian preimplantation embryonic development; b. using the CRISPR-Cas13d RNA-targeting system to modify alternative splicing.

　　Current research projects:

　　1. Alternative splicing (AS) of pre-mRNA is a key component in the regulation of gene expression in mammals and plays an important role in many biological processes. We recently found that UBL5, which affects AS through UBL5-SART1 interaction, was significantly up-expressed in bovine SCNT embryos during embryonic genome activation (EGA) stage. The AS patterns of Ube2g1, a key component of the ubiquitin-binding enzyme E2, had changed during this stage, and the UBL5 dependent 5’splice site (GUGAGU) also found in this gene. But, it is unclear whether UBL5 regulates Ube2g1 alternative splicing and further affects the early development of bovine embryos. In order to validate this hypothesis, this project was designed to study the effect of micropeptide UBL5 on the AS events of Ube2g1 gene by interfering with and overexpressing UBL5. The effects of different spliceosome of Ube2g1 gene on early embryonic development will be analyzed by constructing Ube2g1 gene selective expression vector. This research may provide new insights into revealing the mechanisms of micropeptide protein UBL5 in mammalian embryonic genome activation, and play an important role on bovine preimplantation embryos to overcome developmental block in vitro.

　　2. Alternative splicing (AS) occurs in various developmental processes in mammals. However, studies addressing the functional role of AS in mammalian preimplantation embryonic development are lacking. We recently found that AS has important physiological functions in mammalian preimplantation embryonic development. We discovered abundant AS transitions during key events in preimplantation embryonic development, fertilization, and embryonic genome activation. We also showed that the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNPK) governed the oocyte-to-embryo transition by regulating MII oocyte-specific exon exclusion in mice. Bovine somatic cell nuclear transfer (SCNT) embryos demonstrated abnormal alternative splicing compared with in vitro fertilized (IVF) embryos. We used the CRISPR-Cas13d RNA-targeting system to target cis elements of ABI2 pre-mRNA to modify alternative splicing, thus reducing the ratio of abnormal-isoform SCNT embryos and improving the production of cloned cows. Our results advance the understanding of SCNT-mediated reprogramming and its potential applications for both reproductive and therapeutic cloning.

　　PUBLICATIONS

　　Liu Xu, Wang Yongsheng, Guo Wenjiang, Chang Bohao, Liu Jun, Guo Zekun, Quan Fusheng, Zhang Yong*, Zinc-finger nickase-mediated insertion of the lysostaphin gene into the beta-casein locus in cloned cows. Nature Communications, 2013, 4:2565.

　　Liu Xu, Wang Yongsheng, Tian Yuchen, Yu Yuan, Gao Mingqing, Hu Guangdong, Su Feng, Pan Shaohui, Luo Yan, Guo Zekun, Quan Fusheng, Zhang Yong*, Generation of mastitis resistance in cows by targeting human lysozyme gene to β-casein locus using zinc-finger nucleases. Proc. R. Soc. B, 2014, 281:20133368.

　　Xu Liu*, Rui Cheng, Yingmei Wang, Xiaoman Zheng, Mengyun Wang, Jingcheng Zhang, Xin Liu, Yuanpeng Gao, Xupeng Xing, Yongsheng Wang, Song Hua, Jun Liu, Jianmin Su, Mingqing Gao, Fusheng Quan, Zekun Guo, Yong Zhang*: Modification of alternative splicing in bovine SCNT embryos using engineered CRISPR-Cas13d. Science, 2018. (submitted)

　　FUNDING

　　The regulatory mechanism of UBL5 on bovine embryonic genome activation through alternative splicing of Ube2g1. (No. 31802153), National Natural Science Foundation of China , 2019.1-2021.12, Role: PI;

　　Molecular mechanism of UBL5 regulation of early embryonic developmental arrest in cattle. (No. 2018JQ3035), Innovation Project of Science and Technology in Shaanxi Province, 2018.1-2019.12, Role: PI.