Regulation of rRNA synthesis in corneal epithelium

描述（由申请人提供）：我们的长期目标是了解 基底核蛋白在角膜角质形成细胞rRNA转录中的作用。这 知识将有助于阐明调节的机制， 角膜增生！上皮几种转录因子已经被 参与rRNA转录的调节。这些因素， 而且rRNA合成的细胞类型特异性调节因子 仍然知之甚少。Basonuclin是一种锌指蛋白， 在复层上皮的角质形成细胞和睾丸的生殖细胞， 卵巢，很可能是一个细胞类型特异性，和增殖有关 rRNA基因的转录调节因子，这是同类中的第一个。碱性核菌素 在新生儿和成人角膜上皮中检测到。 我们的假设是，basonuclin是正常发育所必需的， 维持小鼠角膜上皮。碱性核蛋白增强rRNA 转录以满足角膜中蛋白质合成的需求 角质形成细胞在发育和伤口愈合期间。以下三 为检验这一假设提出了具体目标： 具体目的1，研究basonuclin +/- ES细胞是否可以形成角膜基质细胞， ROSA小鼠嵌合体中的角质形成细胞。 具体目的2，检测细胞rRNA含量与细胞内RNA含量之间的相关性， 以及在角膜和其它眼组织中基底核蛋白的存在， 眼睛发育 具体目标3，干扰透化细胞中rRNA的转录 角膜角质形成细胞的碱性核蛋白功能的显性阴性试剂。

DESCRIPTION (provided by applicant):Our long-term goal is to understand the role of basonuclin in rRNA transcription in corneal keratinocytes. This knowledge will help the elucidation of the mechanisms that regulate the proliferation of cornea! epithelium. Several transcription factors have been shown to be involved in the regulation of rRNA transcription. These factors, however, are ubiquitous and cell-type specific regulators of rRNA synthesis are still poorly understood. Basonuclin, a zinc finger protein found in abundance in the keratinocytes of stratified epithelia and the germ cells of testis and ovary, is likely to be a cell type-specific, and proliferation-related transcriptional regulator for the rRNA genes, the first of its kind. Basonuclin was detected in the neonatal and adult corneal epithelium. Our hypothesis is that basonuclin is required for the normal development and maintenance of the mouse corneal epithelium. Basonuclin enhances rRNA transcription to fulfill the demand of protein synthesis in corneal keratinocytes during development and wound healing. The following three specific aims are proposed to test this hypothesis: Specific Aim 1, To investigate if basonuclin +/- ES cells can form corneal keratinocytes in ROSA mouse chimeras. Specific Aim 2, To examine the correlation between the cellular rRNA content and the presence of basonuclin in the cornea and other ocular tissues during eye development. Specific Aim 3, To interfere with the rRNA transcription in permeabilized corneal keratinocytes by dominant-negative reagents of basonuclin function.