2020 Vol. 11, No. 11

Pioneer to exploration and construction of Jilin Province's higher medical laboratory education and talent training system
Huiming Han, Xichao Han, Sainan Wu, Baihui Lin, Xu Cheng, Qinlong Hou, Yongmei Li
2020, 11(11): 783-785. doi: 10.1007/s13238-020-00719-5
Current advances
Recent advances in CRISPR research
Baohui Chen, Yuyu Niu, Haoyi Wang, Kejian Wang, Hui Yang, Wei Li
2020, 11(11): 786-791. doi: 10.1007/s13238-020-00704-y
Mapping the epigenetic modifications of DNA and RNA
Lin-Yong Zhao, Jinghui Song, Yibin Liu, Chun-Xiao Song, Chengqi Yi
2020, 11(11): 792-808. doi: 10.1007/s13238-020-00733-7
Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study. Here, we review the recent technological advances in this rapidly evolving field. We focus on high-throughput detection methods and biological findings for these modifications, and discuss questions to be addressed as well. We also summarize third-generation sequencing methods, which enable long-read and single-molecule sequencing of DNA and RNA modification.
Research articles
Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing
Fang Wang, Weiqi Zhang, Qiaoyan Yang, Yu Kang, Yanling Fan, Jingkuan Wei, Zunpeng Liu, Shaoxing Dai, Hao Li, Zifan Li, Lizhu Xu, Chu Chu, Jing Qu, Chenyang Si, Weizhi Ji, Guang-Hui Liu, Chengzu Long, Yuyu Niu
2020, 11(11): 809-824. doi: 10.1007/s13238-020-00740-8
Many human genetic diseases, including HutchinsonGilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Extracellular signal regulated kinase 5 promotes cell migration, invasion and lung metastasis in a FAK-dependent manner
Weiwei Jiang, Fangfang Cai, Huangru Xu, Yanyan Lu, Jia Chen, Jia Liu, Nini Cao, Xiangyu Zhang, Xiao Chen, Qilai Huang, Hongqin Zhuang, Zi-Chun Hua
2020, 11(11): 825-845. doi: 10.1007/s13238-020-00701-1
This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive potential. Importantly, we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser910 site. Mechanistically, ERK5 increased the expression of the transcription factor USF1, which could transcriptionally upregulate FAK expression, resulting in FAK signaling activation to promote cell migration. We also provided evidence that the phosphorylation of FAK at Ser910 was due to ERK5 but not ERK1/2, and we then suggested a role for Ser910 in the control of cell motility. In addition, ERK5 had targets in addition to FAK that regulate epithelial-to-mesenchymal transition and cell motility in cancer cells. Taken together, our findings uncover a cancer metastasis-promoting role for ERK5 and provide the rationale for targeting ERK5 as a potential therapeutic approach.
SIRT5 is important for bacterial infection by regulating insulin secretion and glucose homeostasis
Cuiping Zhang, Ke Wang, Zuojian Hu, Lujie Yang, Bin Wei, Shan Li, Xue Qin, Pengyuan Yang, Hongxiu Yu
2020, 11(11): 846-851. doi: 10.1007/s13238-020-00709-7
O-GlcNAc transferase regulates centriole behavior and intraflagellar transport to promote ciliogenesis
Fan Yu, Te Li, Yanchao Sui, Qingxia Chen, Song Yang, Jia Yang, Renjie Hong, Dengwen Li, Xiumin Yan, Wei Zhao, Xueliang Zhu, Jun Zhou
2020, 11(11): 852-857. doi: 10.1007/s13238-020-00746-2