Nuclear pore complexes (NPCs) orchestrate cargo between the cytoplasm and nucleus and regulate chromatin organization. NPC proteins, or nucleoporins (Nups), are required for human immunodeficiency virus type 1 (HIV-1) gene expression and genomic integration of viral DNA. We utilize the Ty1 retrotransposon of Saccharomyces cerevisiae (S. cerevisiae) to study retroviral integration because retrotransposons are the progenitors of retroviruses and have conserved integrase (IN) enzymes. Ty1-IN targets Ty1 elements into the genome upstream of RNA polymerase (Pol) III transcribed genes such as transfer RNA (tRNA) genes. Evidence that S. cerevisiae tRNA genes are recruited to NPCs prompted our investigation of a functional role for the NPC in Ty1 targeting into the genome. We find that Ty1 mobility is reduced in multiple Nup mutants that cannot be accounted for by defects in Ty1 gene expression, cDNA production or Ty1-IN nuclear entry. Instead, we find that Ty1 insertion upstream of tRNA genes is impaired. We also identify Nup mutants with wild type Ty1 mobility but impaired Ty1 targeting. The NPC nuclear basket, which interacts with chromatin, is required for both Ty1 expression and nucleosome targeting. Deletion of components of the NPC nuclear basket causes mis-targeting of Ty1 elements to the ends of chromosomes.

中文翻译：

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酵母Ty1反转录转座子需要核孔复合体的成分才能进行转录和基因组整合

核孔复合物（NPC）协调细胞质和细胞核之间的货物并调节染色质的组织。NPC蛋白或核孔蛋白（Nups）是人类1型免疫缺陷病毒（HIV-1）基因表达和病毒DNA的基因组整合所必需的。我们利用酿酒酵母（S. cerevisiae）的Ty1逆转录转座子来研究逆转录病毒整合，因为逆转座子是逆转录病毒的祖先，并且具有整合酶（IN）的保守性。Ty1-IN将Ty1元素靶向RNA聚合酶（Pol）III转录的基因（如转移RNA（tRNA）基因）上游的基因组。酿酒酵母的证据tRNA基因被募集到NPC促使我们调查了NPC在将Ty1靶向基因组中的功能。我们发现，Ty1迁移率在多个Nup突变体中降低，这不能通过Ty1基因表达，cDNA产生或Ty1-IN核进入缺陷来解释。相反，我们发现tRNA基因上游的Ty1插入受到损害。我们还确定了野生型Ty1流动性但受损Ty1靶向的Nup突变体。Ty1表达和核小体靶向都需要与染色质相互作用的NPC核篮。删除NPC核篮的成分会导致Ty1元素错误地定位到染色体末端。