Journal of Genetics and Genomics

mTOR-S6K1 pathway mediates cytoophidium assembly

Zhe Sun, Ji-Long Liu

2019, 46(2): 65-74. doi: 10.1016/j.jgg.2018.11.006

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Abstract:
CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing mTOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.

The genome-wide landscape of small insertion and deletion mutations in Monopterus albus

Feng Chen, Fengling Lai, Majing Luo, Yu-San Han, Hanhua Cheng, Rongjia Zhou

2019, 46(2): 75-86. doi: 10.1016/j.jgg.2019.02.002

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Abstract:
Insertion and deletion (indel) mutations, which can trigger single nucleotide substitutions on the flanking regions of genes, may generate abundant materials for disease defense, reproduction, species survival and evolution. However, genetic and evolutionary mechanisms of indels remain elusive. We establish a comparative genome-transcriptome-alignment approach for a large-scale identification of indels inMonopterus population. Over 2000 indels in 1738 indel genes, including 1–21 bp deletions and 1–15 bp insertions, were detected. Each indel gene had ∼1.1 deletions/insertions, and 2–4 alleles in population. Frequencies of deletions were prominently higher than those of insertions on both genome and population levels. Most of the indels led to in frame mutations with multiples of three and majorly occurred in non-domain regions, indicating functional constraint or tolerance of the indels. All indel genes showed higher expression levels than non-indel genes during sex reversal. Slide window analysis of global expression levels in gonads showed a significant positive correlation with indel density in the genome. Moreover, indel genes were evolutionarily conserved and evolved slowly compared to non-indel genes. Notably, population genetic structure of indels revealed divergent evolution of Monopterus population, as bottleneck effect of biogeographic isolation by Taiwan Strait, China.

Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons

Tao Tao, Jie Sun, Yajing Peng, Pei Wang, Xin Chen, Wei Zhao, Yeqiong Li, Lisha Wei, Wei Wang, Yanyan Zheng, Ye Wang, Xuena Zhang, Min-Sheng Zhu

2019, 46(2): 87-96. doi: 10.1016/j.jgg.2019.02.003

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Abstract:
As a critical guanine nucleotide exchange factor (GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and RhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons (CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth. Such a retardation was reproduced by inhibition of GEF1 domain or knockdown of Cdc42 and restored apparently by introduction of active Cdc42. As Rac1 deficiency did not affect the neurite outgrowth of CGNs, we suggested that Trio GEF1-mediated Cdc42 activation was required for neurite outgrowth. We established a GEF2-knockout line with deletion of all Trio isoforms except a cerebella-specific Trio8, a short isoform of Trio without GEF2 domain, and used this line as a GEF2-deficient animal model. The GEF2-deficient CGNs had a normal neurite outgrowth but abolished Netrin-1-promoted growth, without affecting Netrin-1 induced Rac1 activation. We thus suggested that Trio GEF1-mediated Cdc42 activation rather than Rac1 activation drives the F-actin dynamics necessary for neurite outgrowth, while GEF2 functions in Netrin-1-promoted neurite elongation. Our results delineated the distinct roles of Trio GEF domains in neurite outgrowth, which is instructive to understand the pathogenesis of clinical Trio-related neurodevelopmental disorders.

Artificial selection drives differential gene expression during pig domestication

Yang Yang, Chaorui Liu, Adeniyi C. Adeola, Xierzhatijiang Sulaiman, Hai-Bing Xie, Ya-Ping Zhang

2019, 46(2): 97-100. doi: 10.1016/j.jgg.2018.09.008

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Abstract:

Targeted knockout of duox causes defects in zebrafish growth, thyroid development, and social interaction

Jong-Su Park, Tae-Ik Choi, Oc-Hee Kim, Ted Inpyo Hong, Woo-Keun Kim, Won-Jae Lee, Cheol-Hee Kim

2019, 46(2): 101-104. doi: 10.1016/j.jgg.2019.01.004

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Abstract:

A single nucleotide substitution at 5′-UTR of GSN1 represses its translation and leads to an increase of grain length in rice

Xia Zhang, Peng Qin, Youlin Peng, Bo Ma, Jiangbo Hu, Shijun Fan, Binhua Hu, Guohua Zhang, Hua Yuan, Wei Yan, Weilan Chen, Bin Tu, Hang He, Bingtian Ma, Yuping Wang, Shigui Li

2019, 46(2): 105-108. doi: 10.1016/j.jgg.2019.02.001

Abstract (118) HTML PDF (3)

Abstract:

2019 Vol. 46, No. 2