Selective control of tRNA gene transcription by steroid receptors and BRCA1

类固醇受体和 BRCA1 对 tRNA 基因转录的选择性控制

• 批准号: 2444175
• 金额: --
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2444175
• 关键词: Selective; control; tRNA; gene; transcription

BRCA1 is an important tumour suppressor protein with roles in DNA repairand transcription. BRCA1 binds many tRNA genes, but its role there isunknown. This project will test if repression of tRNA gene transcription byBRCA1 is part of its function as a tumour suppressor.Oestrogen drives proliferation of breast cells and its receptor is targeted bythe widely-used drug tamoxifen. Oestrogen receptor binds and activatestRNA genes, effects that are countered by tamoxifen. Progesterone can alsoantagonize the mitogenic effects of oestrogen. The progesterone receptorwas recently found to interact with RNA polymerase III at specific tRNAgenes and repress their expression. We will investigate how oestrogen andprogesterone receptors select tRNA genes and influence transcription atthese sites.This project will provide extensive training in molecular interactions betweenkey genes and factors with massive impact on cell biology and human health.

BRCA1 是一种重要的肿瘤抑制蛋白，在 DNA 修复和转录中发挥作用。 BRCA1 结合许多 tRNA 基因，但其作用尚不清楚。该项目将测试 BRCA1 对 tRNA 基因转录的抑制是否是其肿瘤抑制功能的一部分。雌激素驱动乳腺细胞增殖，其受体是广泛使用的药物他莫昔芬的靶点。雌激素受体结合并激活stRNA基因，他莫昔芬可以抵消这种作用。黄体酮还可以拮抗雌激素的促有丝分裂作用。最近发现孕酮受体与特定 tRNA 基因上的 RNA 聚合酶 III 相互作用并抑制其表达。我们将研究雌激素和孕激素受体如何选择 tRNA 基因并影响这些位点的转录。该项目将为对细胞生物学和人类健康产生巨大影响的关键基因和因子之间的分子相互作用提供广泛的培训。