Influence of perturbed ribosome assembly on transcription and pre-mRNA splicing in crosstalk with the oncogenes MDM2 and MDM4 (P08)

受干扰的核糖体组装对转录和前 mRNA 剪接与癌基因 MDM2 和 MDM4 串扰的影响 (P08)

• 批准号: 515952419
• 金额: --
• 依托单位: Institute for Molecular Oncology
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/515952419?language=en
• 关键词: Influence; perturbed; ribosome; assembly; transcription

This project addresses the impact of dysbalanced ribosome assembly on transcription and splicing, with a focus on the tumor suppressor p53 and its antagonists MDM2 and MDM4. We have observed that a complex of the 5S RNP and the MDM2 oncoprotein limits the activity of RNA Polymerase III to synthesize 5S rRNA. Moreover, the ribosomal protein eL22/RPL22 binds a specific stem-loop structure within intronic RNA to induce exon skipping of the MDM4 mRNA. We will explore how these regulatory mechanisms affect global gene expression and splicing patterns, and the synthesis of ribosome components.

该项目旨在研究核糖体组装失衡对转录和剪接的影响，重点关注肿瘤抑制因子p53及其拮抗剂MDM 2和MDM 4。我们已经观察到，5S RNP和MDM 2癌蛋白的复合物限制了RNA聚合酶III合成5S rRNA的活性。此外，核糖体蛋白eL 22/RPL 22结合内含子RNA内的特定茎环结构以诱导MDM 4 mRNA的外显子跳跃。我们将探讨这些调控机制如何影响全球基因表达和剪接模式，以及核糖体成分的合成。