Ribosomes and Growth Regulation

核糖体和生长调节

• 批准号: 9160502
• 负责人: Nicholas E Baker
• 金额: $ 30.9万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-08 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9160502
• 关键词: Affect; Anabolism; Aneuploid Cells; Animals; Cancer Etiology; Cell Cycle; Cell Proliferation; Cell Size; Cell Survival; Cells; Childhood; Cirrhosis; DNA Sequence; Defect; Development; Diamond; Diamond-Blackfan anemia; Disease; Drosophila genus; Essential Genes; Exhibits; Feedback; Gene Dosage; Gene Expression; Gene Targeting; Gene-Modified; Genes; Genetic; Genetic Transcription; Genetic study; Genome; Genotype; Growth; Growth and Development function; Heart Diseases; Heart Hypertrophy; Heterozygote; Histocompatibility Testing; Human; Immunohistochemistry; Inherited; Label; Lead; Longevity; Maintenance; Malignant Neoplasms; Mandibulofacial Dysostosis; Maps; Microscopy; Modeling; Molecular Genetics; Mutation; Neurofibromin 2; North American Indians; Northern Blotting; Nucleic Acid Regulatory Sequences; Organ; Organism; Pathway interactions; Process; Protein Biosynthesis; Regulation; Resistance; Resolution; Ribosomal Proteins; Ribosomal RNA; Ribosomes; Role; Spleen; Syndrome; Testing; Tissues; Translations; Transmission Electron Microscopy; bZIP Domain; base; cell fixing; cell growth; cell type; imaginal disc; improved; irradiation; loss of function; macromolecule; mutant; novel; novel therapeutics; overexpression; programs; reproductive; transcription factor; transcriptome; transcriptome sequencing

Ribosomes are responsible for protein synthesis and therefore necessary for the growth of all organs, in both normal development and in disease conditions such as cancer or cardiac hypertrophy. A number of congenital conditions, collectively termed ribosomopathies, result from defects in components of the ribosome or affect its biosynthesis. It is unclear why ribosomopathies have such distinct effects from one another, and it is unclear why mutations in ribosomal genes can cause cancer, since they are required for growth. Reducing the number of ribosomal genes reduces growth rate but surprisingly this has been found to be mainly due to the activation of a new, previously unstudied gene that is believed to encode a transcription factor. To understand how growth is affected, the target genes of this new transcription factor will be identified using a combination of genetic and molecular genetic studies that are possible in the fruitfly. To understand how the new pathway responds to ribosomal protein gene copy number, the DNA sequences that react to such changes will be mapped and characterized. The effect of ribosomal protein gene copy changes on the number of ribosomes, and on the accumulation of their assembly intermediates will be determined to indicate how gene expression is most likely affected. To explore what advantage might accrue from a pathway that slows growth and development, the implications for cell competition, the maintenance of cell size, and for organismal longevity, resistance to genome damage, and body symmetry will be assessed. Given that ribosomes are essential components of all cells, the results of these basic studies are likely to improve understanding of growth in all organs, and diseases that affect growth including cancer, heart disease, and ribosomopathies.

核糖体负责蛋白质合成，因此是生长所必需的 所有器官，无论是在正常发育还是在癌症或癌症等疾病状态下 心脏肥大。许多先天性疾病统称为 核糖体病，由核糖体成分缺陷引起或影响其 生物合成。目前尚不清楚为什么核糖体病与核糖体病具有如此不同的影响 另一个，目前还不清楚为什么核糖体基因突变会导致癌症，因为 它们是成长所必需的。减少核糖体基因的数量会降低生长速度 但令人惊讶的是，这主要是由于新的激活， 以前未被研究过的基因，被认为编码转录因子。到 了解生长如何受到影响，这种新转录因子的靶基因将 通过结合遗传和分子遗传学研究来确定 在果蝇中是可能的。了解新途径如何响应核糖体 蛋白质基因拷贝数，对这种变化做出反应的DNA序列将是 绘制并表征。核糖体蛋白基因拷贝变化对 核糖体的数量及其组装中间体的积累将是 确定表明基因表达最有可能如何受到影响。探索什么 优势可能会从减缓增长和发展的途径中产生， 对细胞竞争、细胞大小的维持以及有机体的影响 将评估寿命、对基因组损伤的抵抗力和身体对称性。给定 核糖体是所有细胞的重要组成部分，这些基础研究的结果 可能会增进对所有器官生长以及影响疾病的了解 生长，包括癌症、心脏病和核糖病。