McGraw Adam P, Bevilacqua Philip C, Babitzke Paul
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
RNA. 2007 Nov;13(11):2020-33. doi: 10.1261/rna.719507. Epub 2007 Sep 19.
TRAP regulates expression of the Bacillus subtilis trpEDCFBA operon by a transcription attenuation mechanism in which tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the nascent trp leader transcript. Bound TRAP blocks formation of an antiterminator structure and allows formation of an overlapping intrinsic terminator upstream of the trp operon structural genes. A 5' stem-loop (5'SL) structure located upstream of the triplet repeat region also interacts with TRAP. TRAP-5'SL RNA interaction participates in the transcription attenuation mechanism by preferentially increasing the affinity of TRAP for the nascent trp leader transcript during the early stages of transcription, when only a few triplet repeats have been synthesized. Footprinting assays indicated that the 5'SL contacts TRAP through two discrete groups of single-stranded nucleotides that lie in the hairpin loop and in an internal loop. Filter binding and in vivo expression assays of 5'SL mutants established that G7, A8, and A9 from the internal loop, and A19 and G20 from the hairpin loop are critical for proper 5'SL function. These nucleotides are conserved among certain other 5'SL-containing organisms. Single-round transcription results indicated that the 5'SL increases the termination efficiency when transcription is fast; however, the influence of the 5'SL was lost when transcription was slowed by reducing the ribonucleoside triphosphate concentration. Since there is a limited amount of time for TRAP to bind to the nascent transcript and promote termination, our data suggest that the contribution of TRAP-5'SL interaction increases the rate of TRAP binding, which, in turn, increases the efficiency of transcription termination.
TRAP通过转录衰减机制调控枯草芽孢杆菌trpEDCFBA操纵子的表达,在该机制中,色氨酸激活的TRAP与新生trp前导转录本中的11个(G/U)AG重复序列结合。结合的TRAP会阻止抗终止子结构的形成,并允许在trp操纵子结构基因上游形成重叠的固有终止子。位于三联体重复区域上游的5'茎环(5'SL)结构也与TRAP相互作用。TRAP-5'SL RNA相互作用通过在转录早期优先增加TRAP对新生trp前导转录本的亲和力来参与转录衰减机制,此时仅合成了少数三联体重复序列。足迹分析表明,5'SL通过位于发夹环和内部环中的两组离散单链核苷酸与TRAP接触。5'SL突变体的滤膜结合和体内表达分析表明,内部环中的G7、A8和A9以及发夹环中的A19和G20对于5'SL的正常功能至关重要。这些核苷酸在某些其他含5'SL的生物体中是保守的。单轮转录结果表明,当转录速度较快时,5'SL会提高终止效率;然而,当通过降低核糖核苷三磷酸浓度使转录速度减慢时,5'SL的影响就会消失。由于TRAP与新生转录本结合并促进终止的时间有限,我们的数据表明,TRAP-5'SL相互作用的作用是提高TRAP的结合速率,进而提高转录终止效率。