Trans-splicing an antibiotic resistant gene to produce a human protein

Transcripts derived from antibiotic resistant genes have been identified in human cells, where they can affect expression of the cellular gene through a novel exogenous-endogenous (exo-endo) trans-splicing, according to research “Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene” published online in Cell Research on July 9^th, 2013.

Prof. LI Boliang and his colleagues at Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, show that through an exo-endo trans-splicing, the chimeric mRNA can be generated from the exogenous transcript derived from recombinant ampicillin-resistant plasmids and the endogenous human mRNA, which is presumably processed through a prior event of interchromosornal trans-splicing, and produces an extra isoform of a key enzyme ACAT1 for the cellular homeostasis of cholesterol. They demonstrate that DNA fragments containing the exogenous sequence with a cryptic promoter and corresponding transcripts from recombinant ampicillin-resistant plasmids have been detected in human blood cells and cell lines.

Antibiotic resistant genes, presenting in natural environments and human intestines with widespread dissemination, are becoming an important challenge of public health, but the presence of antibiotic resistant genes in human tissue cells has hardly been documented. These findings shed light on an exo-endo trans-splicing system, in which antibiotic resistant gene-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.

This work has been selected as the cover story for Cell Research on Aug 2013.