Proudfoot Nick J
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Science. 2016 Jun 10;352(6291):aad9926. doi: 10.1126/science.aad9926.
Terminating transcription is a highly intricate process for mammalian protein-coding genes. First, the chromatin template slows down transcription at the gene end. Then, the transcript is cleaved at the poly(A) signal to release the messenger RNA. The remaining transcript is selectively unraveled and degraded. This induces critical conformational changes in the heart of the enzyme that trigger termination. Termination can also occur at variable positions along the gene and so prevent aberrant transcript formation or intentionally make different transcripts. These may form multiple messenger RNAs with altered regulatory properties or encode different proteins. Finally, termination can be perturbed to achieve particular cellular needs or blocked in cancer or virally infected cells. In such cases, failure to terminate transcription can spell disaster for the cell.
对于哺乳动物的蛋白质编码基因而言,终止转录是一个极其复杂的过程。首先,染色质模板会在基因末端减缓转录。然后,转录本在聚腺苷酸化信号处被切割,以释放信使核糖核酸。剩余的转录本会被选择性地解开并降解。这会在酶的核心部位引发关键的构象变化,从而触发终止。终止也可能发生在基因沿线的可变位置,进而防止异常转录本的形成,或者有意产生不同的转录本。这些转录本可能形成具有改变的调控特性的多个信使核糖核酸,或者编码不同的蛋白质。最后,终止过程可能会受到干扰以满足特定的细胞需求,或者在癌症或病毒感染的细胞中被阻断。在这种情况下,转录无法终止可能会给细胞带来灾难。