Coupling of N7-methyltransferase and 3′-5′ exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading

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The Unique GGA Clathrin Adaptor of Drosophila melanogaster Is Not Essential

The Golgi-localized, γ-ear-containing, ARF binding proteins (GGAs) are a highly conserved family of monomeric clathrin adaptor proteins implicated in clathrin-mediated protein sorting between the trans-Golgi network and endosomes. GGA RNAi knockdowns in Drosophila have resulted in conflicting data concerning whether the Drosophila GGA (dGGA) is essential. The goal of this study was to define the null phenotype for the unique Drosophila GGA. We describe two independently derived dGGA mutations. Neither allele expresses detectable dGGA protein. Homozygous and hemizygous flies with each allele are viable and fertile. In contrast to a previous report using RNAi knockdown, GGA mutant flies show no evidence of age-dependent retinal degeneration or cathepsin missorting. Our results demonstrate that several of the previous RNAi knockdown phenotypes were the result of off-target effects. However, GGA null flies are hypersensitive to dietary chloroquine and to starvation, implicating GGA in lysosomal function and autophagy.     

Screening and Identification of Marburg Virus Entry Inhibitors Using Approved Drugs

正Dear Editor,Marburg virus(MARV) belongs to the Filoviridae family,along with the related Ebola virus(EBOV). Although MARV is less renowned than EBOV, it causes an equally devastating disease, with clinical symptoms similar to EBOV infection and a remarkably high mortality rate. To     

Genetic diversity and relationship of Fritillaria thunbergii Miq. landraces and related taxa

Genetic diversity and differentiation of four landraces of Fritillaria thunbergii Miq. and two congeners Fritillaria cirrhosa D. Don and Fritillaria anhuiensis S. C. Chen et S. F. Yin were evaluated using ISSR markers. The results showed that the genetic diversity of F. thunbergii was high at the specie level but relatively lower at the landrace level. A high level of genetic differentiation among four F. thunbergii landraces was detected based on the gene differentiation coefficient and the AMOVA, in line with the low inter-landrace gene flow. MS-tree analysis showed that the four F. thunbergii landraces were clustered on adjacent positions of the tree, and that Kuanye (Ft-KY) landrace was relatively distantly related to other landraces. In line with the MS-tree analysis, PCoA revealed that the three species of Fritillaria can be divided into two groups and three subgroups, among which there occurred a remarkable genetic differentiation.     

Declined miR‐181a‐5p expression is associated with impaired natural killer cell development and function with aging

MicroRNAs (miRNAs) regulate gene expression and thereby influence cell development and function. Numerous studies have shown the significant roles of miRNAs in regulating immune cells including natural killer (NK) cells. However, little is known about the role of miRNAs in NK cells with aging. We previously demonstrated that the aged C57BL/6 mice have significantly decreased proportion of mature (CD27⁻CD11b⁺) NK cells compared with young mice, indicating impaired maturation of NK cells with aging. Here, we performed deep sequencing of CD27⁺ NK cells from young and aged mice. Profiling of the miRNome (global miRNA expression levels) revealed that 49 miRNAs displayed a twofold or greater difference in expression between young and aged NK cells. Among these, 30 miRNAs were upregulated and 19 miRNAs were downregulated in the aged NK cells. We found that the expression level of miR‐l8la‐5p was increased with the maturation of NK cells, and significantly decreased in NK cells from the aged mice. Knockdown of miR‐181a‐5p inhibited NK cell development in vitro and in vivo. Furthermore, miR‐181a‐5p is highly conserved in mice and human. MiR‐181a‐5p promoted the production of IFN‐γ and cytotoxicity in stimulated NK cells from both mice and human. Importantly, miR‐181a‐5p level markedly decreased in NK cells from PBMC of elderly people. Thus, our results demonstrated that the miRNAs profiles in NK cells change with aging, the decreased level of miR‐181a‐5p contributes to the defective NK cell development and function with aging. This opens new strategies to preserve or restore NK cell function in the elderly.