Bentley David L
Dept. Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, PO Box 6511, Aurora, CO 80045, USA.
J Mol Biol. 2025 Jan 1;437(1):168743. doi: 10.1016/j.jmb.2024.168743. Epub 2024 Aug 9.
Eukaryotic genomes are widely transcribed by RNA polymerase II (pol II) both within genes and in intergenic regions. POL II elongation complexes comprising the polymerase, the DNA template and nascent RNA transcript must be extremely processive in order to transcribe the longest genes which are over 1 megabase long and take many hours to traverse. Dedicated termination mechanisms are required to disrupt these highly stable complexes. Transcription termination occurs not only at the 3' ends of genes once a full length transcript has been made, but also within genes and in promiscuously transcribed intergenic regions. Termination at these latter positions is termed "premature" because it is not triggered in response to a specific signal that marks the 3' end of a gene, like a polyA site. One purpose of premature termination is to remove polymerases from intergenic regions where they are "not wanted" because they may interfere with transcription of overlapping genes or the progress of replication forks. Premature termination has recently been appreciated to occur at surprisingly high rates within genes where it is speculated to serve regulatory or quality control functions. In this review I summarize current understanding of the different mechanisms of premature termination and its potential functions.
真核生物基因组在基因内部和基因间区域广泛由RNA聚合酶II(pol II)转录。包含聚合酶、DNA模板和新生RNA转录本的POL II延伸复合物必须具有极高的持续合成能力,以便转录长度超过1兆碱基且需要数小时才能转录完成的最长基因。需要专门的终止机制来破坏这些高度稳定的复合物。转录终止不仅在生成全长转录本后发生在基因的3'末端,也发生在基因内部以及转录杂乱的基因间区域。在这些后一种位置的终止被称为“过早”,因为它不是由标记基因3'末端的特定信号(如多聚腺苷酸化位点)触发的。过早终止的一个目的是将聚合酶从基因间区域去除,因为在这些区域它们是“不需要的”,因为它们可能会干扰重叠基因的转录或复制叉的进程。最近人们认识到,过早终止在基因内部以惊人的高频率发生,据推测它具有调节或质量控制功能。在这篇综述中,我总结了目前对过早终止的不同机制及其潜在功能的理解。