The Functions of antisense RNA AS-RBM15 in hematopoiesis

反义RNA AS-RBM15在造血中的作用

• 批准号: 9260162
• 负责人: Xinyang Zhao
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9260162
• 关键词: 5' Untranslated Regions; Address; Binding Proteins; Biological Assay; Biological Process; Blood; Bone Marrow Cells; Bone Marrow Transplantation; Cell Line; Cells; Code; Defect; Development; Elements; Genes; Goals; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Homeobox Genes; Human; Human Genome; Knock-out; Knockout Mice; Knowledge; Length; Maps; Mediating; Megakaryocytes; Messenger RNA; Metabolic stress; Methods; Mission; Molecular; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Open Reading Frames; Pathway interactions; Proteins; RNA Splicing; RUNX1 gene; Regulation; Reporting; Research; Role; Signal Transduction; Stress; Subfamily lentivirinae; Subgroup; TP53 gene; Thrombopoietin; Transcriptional Regulation; Translations; Untranslated RNA; WT1 gene; attenuation; biological adaptation to stress; differential expression; in vivo; knock-down; leukemia; mouse model; novel; overexpression; response; self-renewal; small hairpin RNA

Project abstract: The number of long noncoding RNA (lncRNA) genes almost equals to the number of protein coding genes. However, the functions of most of lncRNA genes are unknown. Differential expression of lncRNA genes in different hematopoietic lineages implies that lncRNA genes are important regulators for hematopoiesis. One subgroup of lncRNA genes consists of antisense RNA genes that are transcribed in the opposite direction of their sense counterparts. Many genes important for hematopoiesis such as RBM15, PU.1, WT1, p53 and RUNX1 have antisense counterparts. In this proposed study, we plan to investigate the molecular details on how an antisense RNA (AS-RBM15) of RBM15 gene regulates hematopoiesis. We reported that AS-RBM15 promotes RBM15 protein translation via interaction with the 5'UTR of RBM15 mRNA. Furthermore, AS-RBM15 may promote megakaryocyte differentiation via RBM15-dependent and RBM15-independent pathways. We plan to address the hypothesis that AS-RBM15 regulates hematopoiesis via enhancing protein translation. 1) Determine how the cytoplasmic AS-RBM15 regulates RBM15 protein translation in hematopoietic cells. In this specific aim, we plan to understand how the RNA-RNA interaction involving AS-RBM15 and uORF in 5'UTR of RBM15 mRNA regulates RBM15 protein translation, and what kind of hematopoietic signals regulate AS-RBM15-mediated protein translation. 2) Determine the in vivo biological functions of mouse AS-Rbm15 in hematopoiesis. Although the primary RNA sequences between humans and mice are very different, the biological functions of AS-RBM15 genes may still be conserved. We plan to use mouse leukemia cell lines to investigate AS-Rbm15's molecular functions and to use bone marrow transplantation assays to investigate hematopoiesis in vivo. Accomplishing this proposal will provide us with new paradigms on RNA-mediated regulation, establish methods to study other antisense RNA genes and open up new avenues to understand the roles of long noncoding RNA in normal hematopoiesis.

项目摘要： 长链非编码RNA（longnoncodingRNA，lncRNA）基因的数量几乎等于蛋白质编码基因的数量 基因.然而，大多数lncRNA基因的功能尚不清楚。的差异表达 lncRNA基因在不同的造血谱系中存在，提示lncRNA基因是重要的调控因子 用于造血。lncRNA基因的一个亚组由反义RNA基因组成， 转录方向与它们的感觉对应物相反。许多基因对 例如RBM 15、PU.1、WT 1、p53和RUNX 1具有反义对应物。在这 在这项研究中，我们计划研究反义RNA（AS-RBM 15）的分子细节， RBM 15基因调控造血。我们报道AS-RBM 15促进RBM 15蛋白 通过与RBM 15 mRNA的5 'UTR相互作用翻译。此外，AS-RBM 15可以促进 巨核细胞分化通过RBM 15依赖性和RBM 15非依赖性途径。我们计划 解决AS-RBM 15通过增强蛋白质翻译调节造血的假设。第一章 确定细胞质AS-RBM 15如何调节造血细胞中RBM 15蛋白的翻译 细胞在这个特定的目标，我们计划了解如何RNA-RNA相互作用涉及AS-RBM 15 RBM 15 mRNA的5 'UTR中的uORF调节RBM 15蛋白的翻译， 造血信号调节AS-RBM 15介导的蛋白质翻译。2)确定体内 小鼠AS-Rbm 15在造血中的生物学功能。虽然初级RNA序列 尽管人类和小鼠之间存在很大差异，但AS-RBM 15基因的生物学功能可能仍然存在 保守的我们计划利用小鼠白血病细胞系来研究AS-Rbm 15的分子功能 并使用骨髓移植试验来研究体内造血。完成 这一建议将为我们提供新的RNA介导调控的范例，建立方法， 研究其他反义RNA基因，为理解长非编码区的作用开辟新的途径。 RNA在正常造血中的作用。