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2019 Vol. 10, No. 2

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It is well accepted that Quorum Sensing (QS) is a vital processin bacteria. Remarkably, a recent report described the use ofa QS system for regulation of entry into lytic or lysogenic cycleby the Bacillus-infecting temperate phages phi3T and SPbeta.AimR, encoding the intracellular receptor of AimP, is predictedto be structurally similar to RRNPP regulators. In this issue,Zhen et al. solved the crystal structure of apo AimR as well asAimR-AimP complex, which provide insights into the molecularmechanism underlying the switch between lytic and lysogeniccycles mediated by this arbitrium system.
Recollection
Ke Hsin Kuo: A distinguished scientist and great mentor
Da-Neng Wang, Lu-Chang Qin
2019, 10(2): 79-86. doi: 10.1007/s13238-018-0589-5
[Abstract](715) [PDF 1249KB](9)
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Research articles
Transcriptional mechanism of IRF8 and PU.1 governs microglial activation in neurodegenerative condition
Nan Zhou, Kaili Liu, Yue Sun, Ying Cao, Jing Yang
2019, 10(2): 87-103. doi: 10.1007/s13238-018-0599-3
[Abstract](745) [PDF 3841KB](38)
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Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injuryinduced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition.
TMEM43-S358L mutation enhances NF-κBTGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy
Guoxing Zheng, Changying Jiang, Yulin Li, Dandan Yang, Youcai Ma, Bing Zhang, Xuan Li, Pei Zhang, Xiaoyu Hu, Xueqiang Zhao, Jie Du, Xin Lin
2019, 10(2): 104-119. doi: 10.1007/s13238-018-0563-2
[Abstract](713) [PDF 2365KB](579)
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Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.
Cryo-EM structure of an early precursor of large ribosomal subunit reveals a half-assembled intermediate
Dejian Zhou, Xing Zhu, Sanduo Zheng, Dan Tan, Meng-Qiu Dong, Keqiong Ye
2019, 10(2): 120-130. doi: 10.1007/s13238-018-0526-7
[Abstract](804) [PDF 2933KB](854)
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Assembly of eukaryotic ribosome is a complicated and dynamic process that involves a series of intermediates. It is unknown how the highly intertwined structure of 60S large ribosomal subunits is established. Here, we report the structure of an early nucleolar pre-60S ribosome determined by cryo-electron microscopy at 3.7 Å resolution, revealing a half-assembled subunit. Domains I, Ⅱ and VI of 25S/5.8S rRNA pack tightly into a native-like substructure, but domains Ⅲ, IV and V are not assembled. The structure contains 12 assembly factors and 19 ribosomal proteins, many of which are required for early processing of large subunit rRNA. The Brx1-Ebp2 complex would interfere with the assembly of domains IV and V. Rpf1, Mak16, Nsa1 and Rrp1 form a cluster that consolidates the joining of domains I and Ⅱ. Our structure reveals a key intermediate on the path to establishing the global architecture of 60S subunits.
Letters
Structural basis of AimP signaling molecule recognition by AimR in Spbeta group of bacteriophages
Xiangkai Zhen, Huan Zhou, Wei Ding, Biao Zhou, Xiaolong Xu, Vanja Perčulija, Chun-Jung Chen, Ming-Xian Chang, Muhammad Iqbal Choudhary, Songying Ouyang
2019, 10(2): 131-136. doi: 10.1007/s13238-018-0588-6
[Abstract](587) [PDF 1856KB](30)
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Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2
Guangshun Zhang, Junyuan Cao, Yan Cai, Yang Liu, Yanli Li, Peilin Wang, Jiao Guo, Xiaoying Jia, Mengmeng Zhang, Gengfu Xiao, Yu Guo, Wei Wang
2019, 10(2): 137-142. doi: 10.1007/s13238-018-0604-x
[Abstract](628) [PDF 3556KB](24)
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Down-regulation of the let-7i facilitates gastric cancer invasion and metastasis by targeting COL1A1
Yue Shi, Zipeng Duan, Xun Zhang, Xiaotian Zhang, Guoqing Wang, Fan Li
2019, 10(2): 143-148. doi: 10.1007/s13238-018-0550-7
[Abstract](722) [PDF 1479KB](335)
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The structure differences of Japanese encephalitis virus SA14 and SA14-14-2 E proteins elucidate the virulence attenuation mechanism
Xinyu Liu, Xin Zhao, Rui Na, Lili Li, Eberhard Warkentin, Jennifer Witt, Xu Lu, Yongxin Yu, Yuquan Wei, Guohong Peng, Yuhua Li, Junzhi Wang
2019, 10(2): 149-153. doi: 10.1007/s13238-018-0551-6
[Abstract](676) [PDF 1136KB](534)
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Correction
Correction to: Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg-/- mice
Yaqin Du, Ting Wang, Jun Xu, Chaoran Zhao, Haibo Li, Yao Fu, Yaxing Xu, Liangfu Xie, Jingru Zhao, Weifeng Yang, Ming Yin, Jinhua Wen, Hongkui Deng
2019, 10(2): 154-155. doi: 10.1007/s13238-018-0571-2
[Abstract](567) [PDF 849KB](287)
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