Molecular mechanisms of integration site selection by Dictyostelium retrotransponsons

盘基网柄菌反转录转座子整合位点选择的分子机制

• 批准号: 213735688
• 负责人: Professor Dr. Thomas Winckler
• 金额: --
• 依托单位: Lehrstuhl für Pharmazeutische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/213735688?language=en
• 关键词: Molecular; mechanisms; integration; site; selection

Retrotransposons amplify by producing DNA copies of their own RNA, which then integrate at new sites in the host cell genome. In gene-dense genomes, the actively replicating retrotransposons cause a constant threat of insertional mutagenesis. The genome of the social amoeba Dictyostelium dis-coideum contains retrotransposons that insert preferentially in the vicinity of tRNA genes to avoid insertional mutagenesis of protein-coding genes. Our previous studies on the retrotransposon TRE5-A suggest that specific interactions between a retrotransposon-encoded protein and subunits of the tRNA gene-specific transcription factor TFIIIB mediate integration upstream of tRNA genes. In this project, we will evaluate the hypothesis that two other tRNA gene-specific retrotransposons in the D. discoideum genome also recognize integration sites by protein-protein contacts with tRNA gene-specific transcription factors. We will investigate retrotransposon TRE3-A, which is phylogenetically related to TRE5-A but integrates in the 3' region of tRNA genes, and DGLT-A, which integrates 5' of tRNA genes similar to TRE5-A but belongs to a different retrotransposon group.

反转录转座子通过产生自身RNA的DNA拷贝来扩增，然后在宿主细胞基因组的新位点整合。在基因密集的基因组中，积极复制的逆转录转座子引起插入突变的持续威胁。群居变形虫Dictyostelium dis-coideum的基因组包含逆转录转座子，这些转座子优先插入tRNA基因附近，以避免蛋白质编码基因的插入突变。我们之前对逆转录转座子TRE5-A的研究表明，逆转录转座子编码的蛋白与tRNA基因特异性转录因子TFIIIB亚基之间的特异性相互作用介导了tRNA基因上游的整合。在这个项目中，我们将评估一种假设，即盘状龙脑基因组中另外两个tRNA基因特异性反转录转座子也通过与tRNA基因特异性转录因子的蛋白-蛋白接触来识别整合位点。我们将研究逆转录转座子TRE3-A和DGLT-A，前者在系统发育上与TRE5-A相关，但整合在tRNA基因的3‘区；后者整合了与TRE5-A相似的tRNA基因的5’区，但属于不同的逆转录转座子群。