人长非编码ACAT1C7基因组结构与表达调控及功能

项目名称： 人长非编码ACAT1C7基因组结构与表达调控及功能

项目编号： No.31271377

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 李伯良

作者单位： 中国科学院上海生命科学研究院

项目金额： 110万元

中文摘要： ACAT是细胞内唯一催化游离胆固醇和长链脂肪酸形成胆固醇脂的酶，在胆固醇代谢平衡的生理功能与异常引起AS、AD等病理变化中起重要作用。它定位于内质网膜、含量极低，国际上还未能纯化其天然型酶蛋白，所以通过基因水平研究其功能是目前切实可行途径。本申请项目是在我们前期报道人ACAT1和ACAT2基因组结构、启动子和表达调控等前沿性研究的积累基础上，根据新近研究表明曾报道为人ACAT1基因的7号染色体序列是一个独立的长非编码ACAT1C7基因及其转录RNA可影响ACAT1 mRNA的稳定性等重要线索，集中对长非编码ACAT1C7基因的特异性基因组结构及其与自身表达调控的关系、7号染色体来源长非编码ACAT1C7 RNA 对1号染色体来源ACAT1 mRNA降解的功能作用等进行详细研究，获得成果可为深入阐析长非编码ACAT1C7基因表达的细胞水平功能与跨染色体反式剪接机制等研究奠定极重要的基础。

中文关键词： 长非编码RNA ACAT1C7；ACAT1功能；ACAT1C7基因；Alu序列；胆固醇代谢平衡

英文摘要： Acyl-CoA:cholesterol acyltransferase (ACAT) is the exclusive intracellular enzyme that catalyzes the formation of cholesteryl esters (CE) from long-chain fatty acyl coenzyme A and cholesterol, holding pivotal position in cholesterol homeostasis and correlative diseases such as atherosclerosis (AS) and Alzheimer's disease (AD). ACAT localizes in endoplasmic reticulum with very low content, and up to now no natural ACAT enzyme has been purified to homogeneity, so study at the gene level is the essential practical way for revealing its regulatory expression and role. Based on our previous work that have revealed the genomic organization of ACAT1 and ACAT2 genes as well as their regulatory expressions, and our recent results showing that the reported human ACAT1 gene sequence localized in chromosome 7 is a long non-coding ACAT1C7 gene and affects the stability of human ACAT1 mRNA, this application focuses on the special genomic organization and regulatory expression of human long non-coding ACAT1C7 gene as well as the functional affecting of the chromosome 7-produced long non-coding ACAT1C7 RNA on the chromosome 1-produced ACAT1 mRNA decay. These will provide very important bases for further studies on the cellular function of the long non-coding ACAT1C7 gene expression and mechanism of the interchromosomal trans-sp

英文关键词： Long non-coding RNA ACAT1C7；ACAT1 role；ACAT1C7 gene；Alu sequence；Cholesterol homeostasis