Department of Chemical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9721-6. doi: 10.1073/pnas.1101569108. Epub 2011 May 23.
Convergent gene pairs with head-to-head configurations are widespread in both eukaryotic and prokaryotic genomes and are speculated to be involved in gene regulation. Here we present a unique mechanism of gene regulation due to convergent transcription from the antagonistic prgX/prgQ operon in Enterococcus faecalis controlling conjugative transfer of the antibiotic resistance plasmid pCF10 from donor cells to recipient cells. Using mathematical modeling and experimentation, we demonstrate that convergent transcription in the prgX/prgQ operon endows the system with the properties of a robust genetic switch through premature termination of elongating transcripts due to collisions between RNA polymerases (RNAPs) transcribing from opposite directions and antisense regulation between complementary counter-transcripts. Evidence is provided for the presence of truncated RNAs resulting from convergent transcription from both the promoters that are capable of sense-antisense interactions. A mathematical model predicts that both RNAP collision and antisense regulation are essential for a robust bistable switch behavior in the control of conjugation initiation by prgX/prgQ operons. Moreover, given that convergent transcription is conserved across species, the mechanism of coupling RNAP collision and antisense interaction is likely to have a significant regulatory role in gene expression.
在真核生物和原核生物基因组中,头对头配置的趋同基因对广泛存在,据推测它们参与基因调控。在这里,我们提出了一种由于来自 Enterococcus faecalis 中的拮抗 prgX/prgQ 操纵子的趋同转录而导致的基因调控的独特机制,该操纵子控制抗生素抗性质粒 pCF10 从供体细胞到受体细胞的接合转移。通过数学建模和实验,我们证明了 prgX/prgQ 操纵子中的趋同转录通过来自相反方向的 RNA 聚合酶 (RNAP) 转录之间的碰撞以及互补反向转录物之间的反义调节,赋予该系统具有稳健遗传开关的特性。提供了证据表明,由于来自能够进行反义相互作用的启动子的趋同转录,产生了截短的 RNA。数学模型预测,RNAP 碰撞和反义调节对于 prgX/prgQ 操纵子控制接合起始的稳健双稳态开关行为都是必不可少的。此外,鉴于趋同转录在物种间是保守的,因此,RNAP 碰撞和反义相互作用的耦合机制很可能在基因表达中具有重要的调节作用。