Effectors of retrotransposon movement

逆转录转座子运动的效应器

• 批准号: 9769817
• 负责人: David J. Garfinkel
• 金额: $ 44.01万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769817
• 关键词: Address; Adopted; Affect; Affinity Chromatography; Binding; Biochemical; Biochemistry; Biological; Biological Assay; Biology; CDK6-associated protein p18; Capsid; Capsid Proteins; Cells; Cellular biology; Collaborations; Complementary DNA; Complex; Cryo-electron tomography; Cryoelectron Microscopy; DNA Polymerase III; Data; Defective Viruses; Defense Mechanisms; Dose; Elements; Enzymes; Escape Mutant; Eukaryota; Evolution; GAG Gene; Genes; Genetic; Genome; Genomics; Goals; HIV; HIV-1; Integrase; Left; Long Terminal Repeats; Maps; Mediating; Methods; Molecular Chaperones; Movement; Nature; Nuclear Export; Nucleic Acids; Oncogenic; Parasites; Peptide Hydrolases; Process; Production; Proteins; RNA; RNA Polymerase III; Reading Frames; Recording of previous events; Research; Research Personnel; Resistance; Retroelements; Retrotransposon; Retroviridae; Retrovirology; Reverse Transcription; Role; Saccharomyces; Saccharomyces cerevisiae; Shapes; Sheep; Site; Structure; System; Transcript; Translating; Universities; Variant; Virus; Virus Assembly; Virus-like particle; Work; Yeasts; base; cofactor; flexibility; genome sciences; genomic RNA; genomic data; information model; inhibitor/antagonist; insight; interdisciplinary approach; interest; medical schools; multidisciplinary; new therapeutic target; novel; particle; structural biology; three dimensional structure

PROJECT SUMMARY/ABSTRACT Effectors of retrotransposon movement The retrovirus-like transposon Ty1 of Saccharomyces is an informative model for understanding how retrotransposons and retroviruses mobilize, shape the genome, and interact with host and element encoded factors. The additive nature of the retroelement replication cycle can result in massive increases in copy number if left unchecked. Host cells have countered with several defense systems, including domestication of retroelement genes that now act as restriction factors to minimize propagation. We discovered a truncated form of the Ty1 capsid protein that inhibits virus-like particle assembly and function. This self-encoded restriction factor expands the repertoire of defense proteins targeting the capsid. Our work also highlights an intriguing host-parasite strategy. Instead of inhibiting all transposon movement by domesticating the restriction gene as a distinct locus, yeast and Ty1 may have coevolved a relationship that allows high levels of transposition when copy numbers are low and progressively less transposition as copy numbers rise. Our goal is to understand the mechanism and evolution of Ty1 copy number control by a combination of genetic, genomic, cell biological, biochemical and structural approaches.

项目总结/摘要 反转录转座子运动效应子 酵母属的逆转录病毒样转座子Ty 1是了解如何 逆转录转座子和逆转录病毒移动，塑造基因组，并与宿主和编码元件相互作用 因素逆向元件复制周期的累加性质可以导致复制的大量增加 如果未选中，则为编号。宿主细胞用几种防御系统进行反击，包括驯化细菌。 逆转录因子基因，现在作为限制因素，以尽量减少繁殖。我们发现了一个截短的 抑制病毒样颗粒组装和功能的Ty 1衣壳蛋白的形式。这个自我编码的 限制因子扩大了靶向衣壳的防御蛋白的库。我们的工作还突出了一个 有趣的宿主-寄生虫策略不是通过驯化限制来抑制所有转座子运动， 基因作为一个独特的基因座，酵母和Ty 1可能共同进化的关系，允许高水平的 当拷贝数较低时，转座逐渐减少，而当拷贝数增加时，转座逐渐减少。我们的目标 是了解Ty 1拷贝数控制的机制和进化， 基因组、细胞生物学、生物化学和结构方法。