2019 Vol. 10, No. 9

The RNA component of mammalian telomerase TERC is processed in mitochondria to TERC-53 and then exported back to the cytosol. The cytosolic TERC-53 levels respond to mitochondrial defects. Zheng et al. show that cytosolic TERC-53 regulates cellular senescence and is involved in cognition decline in mouse hippocampus, without affecting telomerase activities. It functions by interfering with nuclear translocation of a transcriptional factor and subsequently changing nuclear gene expression. These findings uncover a mitochondrial retrograde signaling pathway with a non-coding RNA as the signal. The cover picture is a cartoon depiction of a sick mitochondrion communicating with the nucleus. This image was designed and composed by Geng Wang.
Jiao Shao: A forerunner of physiological psychology and comparative psychology in China
Lijun Wang, Yanyan Qian, Yanjie Su
2019, 10(9): 623-627. doi: 10.1007/s13238-018-0592-x
Systematic biomedical research of the NASA Twins Study facilitates the hazard risk assessment of long-term spaceflight missions
Zhongquan Dai, Xiaohua Lei, Chao Yang, Lei Zhao, Liang Lu, Yinghui Li
2019, 10(9): 628-630. doi: 10.1007/s13238-019-0628-x
Research articles
Mitochondrion-processed TERC regulates senescence without affecting telomerase activities
Qian Zheng, Peipei Liu, Ge Gao, Jiapei Yuan, Pengfeng Wang, Jinliang Huang, Leiming Xie, Xinping Lu, Fan Di, Tanjun Tong, Jun Chen, Zhi Lu, Jisong Guan, Geng Wang
2019, 10(9): 631-648. doi: 10.1007/s13238-019-0612-5
Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc-/- cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.
Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis
Xing Zhang, Zunpeng Liu, Xiaoqian Liu, Si Wang, Yiyuan Zhang, Xiaojuan He, Shuhui Sun, Shuai Ma, Ng Shyh-Chang, Feng Liu, Qiang Wang, Xiaoqun Wang, Lin Liu, Weiqi Zhang, Moshi Song, Guang-Hui Liu, Jing Qu
2019, 10(9): 649-667. doi: 10.1007/s13238-019-0610-7
RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.
Core pluripotency factors promote glycolysis of human embryonic stem cells by activating GLUT1 enhancer
Lili Yu, Kai-yuan Ji, Jian Zhang, Yanxia Xu, Yue Ying, Taoyi Mai, Shuxiang Xu, Qian-bing Zhang, Kai-tai Yao, Yang Xu
2019, 10(9): 668-680. doi: 10.1007/s13238-019-0637-9
Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the genome-wide data of binding sites of the core pluripotency factors (SOX2, OCT4, NANOG, denoted SON), chromosomal interaction and histone modification in hESCs, we identified a potential enhancer of the GLUT1 gene in hESCs, denoted GLUT1 enhancer (GE) element. GE interacts with the promoter of GLUT1, and the deletion of GE significantly reduces the expression of GLUT1, glucose uptake and glycolysis of hESCs, confirming that GE is an enhancer of GLUT1 in hESCs. In addition, the mutation of SON binding motifs within GE reduced the expression of GLUT1 as well as the interaction between GE and GLUT1 promoter, indicating that the binding of SON to GE is important for its activity. Therefore, SON promotes glucose uptake and glycolysis in hESCs by inducing GLUT1 expression through directly activating the enhancer of GLUT1.
Structural insights into the species preference of the influenza B virus NS1 protein in ISG15 binding
Yinan Jiang, Xinquan Wang
2019, 10(9): 681-687. doi: 10.1007/s13238-018-0598-4
Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals
Qing-Zhuo Liu, Mei Hao, Zi-Yang Zhou, Jian-Long Ge, Yi-Chen Wu, Ling-Ling Zhao, Xiang Wu, Yi Feng, Hong Gao, Shun Li, Lei Xue
2019, 10(9): 688-693. doi: 10.1007/s13238-019-0624-1
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) contributes to incorporation of histone variant H2A.Z into nucleosomes
Ling-Yao Wang, Yun-xiao He, Min Li, Jian Ding, Yi Sui, Joan W. Conaway, Ronald C. Conaway, Fei Wang, Jingji Jin, Yong Cai
2019, 10(9): 694-699. doi: 10.1007/s13238-019-0632-1
Correction to: Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants
Lei Yang, Xiaohui Zhang, Liren Wang, Shuming Yin, Biyun Zhu, Ling Xie, Qiuhui Duan, Huiqiong Hu, Rui Zheng, Yu Wei, Liangyue Peng, Honghui Han, Jiqin Zhang, Wenjuan Qiu, Hongquan Geng, Stefan Siwko, Xueli Zhang, Mingyao Liu, Dali Li
2019, 10(9): 700-700. doi: 10.1007/s13238-019-0631-2