Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene

	Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene
	Hu, GJ; Chen, J; Zhao, XN; Xu, JJ; Guo, DQ; Lu, M; Zhu, M; Xiong, Y; Li, Q; Chang, CCY
刊名	CELL RESEARCH
	2013
卷号	23 期号:8 页码:1007-1024
关键词	trans-splicing chimeric RNA ampicillin resistance gene recombinant plasmid ACAT1
通讯作者	Li, BL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,blli@sibcb.ac.cn
英文摘要	Trans-splicing, a process involving the cleavage and joining of two separate transcripts, can expand the transcriptome and proteome in eukaryotes. Chimeric RNAs generated by trans-splicing are increasingly described in literatures. The widespread presence of antibiotic resistance genes in natural environments and human intestines is becoming an important challenge for public health. Certain antibiotic resistance genes, such as ampicillin resistance gene (Ampr), are frequently used in recombinant plasmids. Until now, trans-splicing involving recombinant plasmid-derived exogenous transcripts and endogenous cellular RNAs has not been reported. Acyl-CoA: cholesterol acyltransferase 1 (ACAT1) is a key enzyme involved in cellular cholesterol homeostasis. The 4.3-kb human ACAT1 chimeric mRNA can produce 50-kDa and 56-kDa isoforms with different enzymatic activities. Here, we show that human ACAT1 56-kDa isoform is produced from an mRNA species generated through the trans-splicing of an exogenous transcript encoded by the antisense strand of Ampr (asAmp) present in common Ampr-plasmids and the 4.3kb endogenous ACAT1 chimeric mRNA, which is presumably processed through a prior event of interchromosomal trans-splicing. Strikingly, DNA fragments containing the asAmp with an upstream recombined cryptic promoter and the corresponding exogenous asAmp transcripts have been detected in human cells. Our findings shed lights on the mechanism of human ACAT1 56-kDa isoform production, reveal an exogenous-endogenous trans-splicing system, in which recombinant plasmid-derived exogenous transcripts are linked with endogenous cellular RNAs in human cells, and suggest that exogenous DNA might affect human gene expression at both DNA and RNA levels.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	COA-CHOLESTEROL ACYLTRANSFERASE-1 ; 2 DIFFERENT CHROMOSOMES ; MESSENGER-RNA ; ACYL-COENZYME ; IN-VITRO ; NATURAL ENVIRONMENTS ; PROSTATE-CANCER ; DROSOPHILA ; PROTEIN ; DNA
收录类别	SCI
语种	英语
WOS记录号	WOS:000322574900009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/418]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Hu, GJ,Chen, J,Zhao, XN,et al. Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene[J]. CELL RESEARCH,2013,23(8):1007-1024.
APA	Hu, GJ.,Chen, J.,Zhao, XN.,Xu, JJ.,Guo, DQ.,...&Li, BL.(2013).Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene.CELL RESEARCH,23(8),1007-1024.
MLA	Hu, GJ,et al."Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene".CELL RESEARCH 23.8(2013):1007-1024.