Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
Watchmaker Genomics, Boulder, CO, USA.
Nat Microbiol. 2020 Apr;5(4):545-553. doi: 10.1038/s41564-020-0667-3. Epub 2020 Feb 24.
Regulated gene expression is largely achieved by controlling the activities of essential, multisubunit RNA polymerase transcription elongation complexes (TECs). The extreme stability required of TECs to processively transcribe large genomic regions necessitates robust mechanisms to terminate transcription. Efficient transcription termination is particularly critical for gene-dense bacterial and archaeal genomes in which continued transcription would necessarily transcribe immediately adjacent genes and result in conflicts between the transcription and replication apparatuses; the coupling of transcription and translation would permit the loading of ribosomes onto aberrant transcripts. Only select sequences or transcription termination factors can disrupt the otherwise extremely stable TEC and we demonstrate that one of the last universally conserved archaeal proteins with unknown biological function is the Factor that terminates transcription in Archaea (FttA). FttA resolves the dichotomy of a prokaryotic gene structure (operons and polarity) and eukaryotic molecular homology (general transcription apparatus) that is observed in Archaea. This missing link between prokaryotic and eukaryotic transcription regulation provides the most parsimonious link to the evolution of the processing activities involved in RNA 3'-end formation in Eukarya.
基因表达的调控在很大程度上是通过控制必需的多亚基 RNA 聚合酶转录延伸复合物(TEC)的活性来实现的。TEC 必须具有极高的稳定性才能进行大片段基因组区域的连续转录,因此需要有强大的机制来终止转录。对于基因密集的细菌和古菌基因组来说,有效的转录终止尤为关键,如果继续转录,必然会转录紧邻的基因,从而导致转录和复制装置之间发生冲突;转录和翻译的偶联会允许核糖体加载到异常的转录本上。只有特定的序列或转录终止因子才能破坏原本极其稳定的 TEC,我们证明了一种在古菌中具有未知生物学功能的最后一种普遍保守的古菌蛋白是终止古菌转录的因子(FttA)。FttA 解决了原核生物基因结构(操纵子和极性)和真核生物分子同源性(一般转录装置)之间的二分法,这种二分法在古菌中是观察到的。这种原核生物和真核生物转录调控之间缺失的联系,为真核生物 RNA 3' 端形成过程中涉及的加工活性的进化提供了最简约的联系。