Molecular mechanistic studies of long “noncoding” RNAs in mammalian cell differentiation

哺乳动物细胞分化中长“非编码”RNA 的分子机制研究

基本信息

批准号：
10538558
负责人：
Wenqian Hu
金额：
$ 31.8万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10538558
关键词：
Address Amino Acids Antisense RNA Area Automated Annotation Biological Process Biology Categories Cell Differentiation process Cell Maturation Cell Nucleus Cell Size Cells Chromatin Classification Code Collaborations Computational algorithm Confusion DLEU2 gene Discrimination Disease Erythrocytes Erythroid Cells Gene Expression Gene Expression Regulation Genes Genetic Transcription Genomics Goals Homologous Gene Human In Vitro Inflammatory Inflammatory Response Inhibition of Apoptosis Knockout Mice Knowledge Macrophage Malignant Neoplasms Mammalian Cell Mediating Messenger RNA Methods Modeling Molecular Molecular Biology Mus Nuclear Open Reading Frames Pathologic Physical condensation Physiological Play Process Proteins RNA Regulator Genes Ribosomes Role Specificity System Tertiary Protein Structure Transcript Untranslated RNA Work cell type diagnostic biomarker differential expression erythroid differentiation experimental study human disease insight leukemia loss of function mouse model novel polypeptide ribosome profiling stem cells therapeutic target tool transcriptomics

项目摘要

PROJECT SUMMARY The goal of this study is to determine the molecular mechanisms by which long “noncoding” RNAs regulate mammalian cells differentiation. Long noncoding RNAs (lncRNAs), defined as RNAs longer than 200nt without functional protein coding capacity, are emerging regulators of gene expression. Genomic studies revealed that many lncRNAs are differentially expressed in a wide variety of biological processes. Although an increasing number of lncRNAs are observed to play important roles under many physiological and pathological conditions, the molecular mechanisms they use to control gene expression are still unknown for a lot of lncRNAs. Thus, mechanistically characterizing functionally important lncRNAs in mammalian cells is of high significance to both RNA molecular biology and potential usage of these RNAs as diagnostic markers and therapeutic targets. Using the terminal differentiation of erythroid cells as a model, our recent studies revealed that lncRNAs can be classified into bona fide lncRNAs and small-polypeptide-encoding “lncRNAs” based on their functional association with the cellular translational apparatus, the ribosome. Notably, we observed that lncRNAs from each of these two categories play critical roles in this important cell differentiation process. Thus, we plan to mechanistically dissect how bona fide lncRNAs and small-polypeptide-encoding “lncRNAs” regulate gene expression in mammalian cell differentiation, respectively. The results from this study will not only fill a fundamental knowledge gap in lncRNA biology, the molecular mechanisms of lncRNAs, but also may potentially provide insights for human diseases, as one of the lncRNAs we will study, Dleu2, is frequently deleted in certain human leukemias.

项目摘要这项研究的目的是确定长期“非编码” RNA调节的分子机制哺乳动物细胞分化。长的非编码RNA（LNCRNA），定义为RNA，不超过200nt 功能蛋白编码能力是基因表达的新兴调节剂。基因组研究表明许多LNCRNA在各种生物学过程中都有不同的表达。虽然越来越多观察到的lncrnas数量在许多物理和病理条件下都起着重要作用，他们用来控制基因表达的分子机制对于许多LNCRNA仍未知。那，机械地表征哺乳动物细胞中功能上重要的LNCRNA对两者都有很高的意义 RNA分子生物学和这些RNA作为诊断标记和治疗靶标的潜在用法。使用红细胞细胞的末端分化作为模型，我们的最新研究表明，LNCRNA可以是基于其功能，分为真正的lncrNA和小型肽编码的“ lncrnas” 与细胞平移仪的核糖体相关。值得注意的是，我们观察到来自这两个类别中的每一个在这个重要的细胞分化过程中起着关键作用。那我们计划机械学剖析真正的lncrNA和小型肽编码“ lncRNA”调节基因哺乳动物细胞分化中的表达。这项研究的结果不仅会填补 LNCRNA生物学的基本知识差距，LNCRNA的分子机制，但也可以可能提供有关人类疾病的见解，因为我们将研究的LNCRNA之一是DLEU2，通常是在某些人类白血病中删除。