发现干扰细菌基因表达的新途径
2016-05-25来源：未知兰贡医学中心生物化学教授伊夫简尼·努德勒博士表示，有关活性核糖体在各种编码蛋白基因中和不同生长条件下控制转录率的发现出乎他们的意料之外，这是十分难得的收获。他认为，在转译初始转录产物时，核糖体不仅在核糖核酸聚合酶后运动，而且事实上能够“推动”停顿的或被俘的核糖核酸聚合酶，从而加快核糖核酸聚合酶速度，并同时帮助核糖核酸聚合酶穿越脱氧核糖核酸（DNA）结合蛋白质组成的“路障”。
在研究中，努德勒和同事发现，在不同的生长条件下，转录延伸率和转译率完全吻合。他们同时注意到，转录率依赖于调节核糖体速度的密码子使用或稀有密码子频率。此外，他们表示，核糖体的速度决定了核糖核酸聚合酶的速度，通过化学或基因操作让核糖体加速或减速能导致核糖核酸聚合物的速度出现相应的变化。
转录和转译是遗传密码转为蛋白质过程中两个重要步骤。数据显示，这两个步骤紧密耦合在一起，缺少其中任何一个，遗传密码转为蛋白质的过程均无法有效进行。因此，科学家认为，通过有意地阻断核糖核酸聚合酶与核糖体间的物理联系，破坏两个步骤间的耦合，有望成为干扰细菌基因表达的新方法和抗生素治疗的新目标。
Cooperation Between Translating Ribosomes and RNA Polymerase in Transcription
Elongation
Sergey Proshkin1,2 A. Rachid Rahmouni3 Alexander Mironov2 Evgeny Nudler1
1 Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
2 State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia.
3 Centre de Biophysique Moléculaire, CNRS, Rue Charles Sadron, 45071 Orléans, France.
【Abstract】During transcription of protein-coding genes, bacterial RNA polymerase (RNAP) is closely followed by a ribosome that translates the newly synthesized transcript. Our in vivo measurements show that the overall elongation rate of transcription is tightly controlled by the rate of translation. Acceleration and deceleration of a ribosome result in corresponding changes in the speed of RNAP. Moreover, we found an inverse correlation between the number of rare codons in a gene, which delay ribosome progression, and the rate of transcription. The stimulating effect of a ribosome on RNAP is achieved by preventing its spontaneous backtracking, which enhances the pace and also facilitates readthrough of roadblocks in vivo. Such a cooperative mechanism ensures that the transcriptional yield is always adjusted to translational needs at different genes and under various growth conditions.
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