Ribosome Protein Heterogeneity: The basis of wide spread roles for specialized ribosomes in tuning global gene expression.

核糖体蛋白质异质性：特殊核糖体在调节全局基因表达中广泛作用的基础。

• 批准号: RGPIN-2017-05792
• 负责人: Fahlman, Richard
• 金额: $ 2.04万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711485
• 关键词: Ribosome; Protein; Heterogeneity; basis; wide

The traditional view of the ribosome is where each large and small ribosomal subunit is composed of its ribosomal RNAs and a defined set of ribosomal proteins. Now emerging evidence is beginning to challenge this view of a static universal ribosome structure as it is becoming apparent that different ribosomes can vary in their make-up of many core ribosomal proteins. Recent published data is also revealing the functional implications of variable ribosomal protein composition of ribosomes as there are examples demonstrating the requirement for specific ribosomal proteins for the translation of specific mRNAs. For example, recently published work describes how ribosomes containing Rpl38 are required for the translation of specific Hox genes in specific cells during development. One can envision numerous scenarios how specialized ribosomes which vary in their core ribosomal protein content are tuned for optimal gene expression in different cell types and tissues. Preliminary Data: Following up on previously published data that quantified large differences for some ribosomal protein mRNAs between different murine tissues, we have quantitatively compared the ribosomal proteome of purified ribosomes from some murine tissues and cell lines. Our preliminary data is in agreement with the mRNA expression data where we have also quantified highly variable abundances for several ribosomal proteins while others remain constant. This variability of a subset of ribosomal proteins merits further investigations into the functional implications in gene expression. To further investigate ribosome variability we are pursuing the following Specific Aims: Aim 1) Quantifying Ribosomal Variations: Complete our quantification of the differences in the ribosomal proteome of ribosomes purified from different murine tissues and cell lines. Aim 2) Functional Investigations of Ribosomal Variants: Identify the mRNAs being actively translated in polysomes in the murine 3T3 cell line in the presence and absence of ribosomal proteins that exhibit variable ribosomal occupancy. Aim 3) Mechanistic Investigations of Translational Evasion: Investigate the molecular basis of how these mRNAs under ribosomal specific selective translation are not translated by canonical 5'-cap dependent translation and require specific ribosomal proteins for translation. Impact: The demonstration of the breadth of the role for ribosomes in gene expression by selective mRNA translation would redefine how we view the role of ribosomes in protein synthesis. The identification of ribosomes playing an active role in the regulation of gene expression may be one of the largest overlooked aspects of post transcriptional gene regulation and has the potential to function in numerous regulatory roles in both development and disease.

传统的核糖体观点认为，每个大小核糖体亚基都是由其核糖体rna和一组确定的核糖体蛋白组成的。现在，新出现的证据开始挑战这种静态通用核糖体结构的观点，因为越来越明显，不同的核糖体在许多核心核糖体蛋白的组成上可能有所不同。最近发表的数据也揭示了核糖体的可变核糖体蛋白组成的功能含义，因为有例子表明，特定mrna的翻译需要特定的核糖体蛋白。例如，最近发表的研究描述了含有Rpl38的核糖体是如何在特定细胞发育过程中翻译特定Hox基因所必需的。我们可以设想许多场景，即不同核心核糖体蛋白含量的特化核糖体如何在不同的细胞类型和组织中调整为最佳的基因表达。