Kopczyńska Magda, Saha Upasana, Romanenko Anastasiia, Nojima Takayuki, Gdula Michał R, Kamieniarz-Gdula Kinga
Center for Advanced Technologies, Adam Mickiewicz University, Uniwersytetu Poznanskiego 10, 61-614 Poznan, Poland.
Department of Molecular and Cellular Biology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 6, 61-614 Poznan, Poland.
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1240.
Defining the beginning of a eukaryotic protein-coding gene is relatively simple. It corresponds to the first ribonucleotide incorporated by RNA polymerase II (Pol II) into the nascent RNA molecule. This nucleotide is protected by capping and maintained in the mature messenger RNA (mRNA). However, in higher eukaryotes, the end of mRNA is separated from the sites of transcription termination by hundreds to thousands of base pairs. Currently used genomic annotations only take account of the end of the mature transcript - the sites where pre-mRNA cleavage occurs, while the regions in which transcription terminates are unannotated. Here, we describe the evidence for a marker of transcription termination, which could be widely applicable in genomic studies. Pol II termination regions can be determined genome-wide by detecting Pol II phosphorylated on threonine 4 of its C-terminal domain (Pol II CTD-T4ph). Pol II in this state pauses before leaving the DNA template. Up to date this potent mark has been underused because the evidence for its place and role in termination is scattered across multiple publications. We summarize the observations regarding Pol II CTD-T4ph in termination regions and present bioinformatic analyses that further support Pol II CTD-T4ph as a global termination mark in animals.
定义真核生物蛋白质编码基因的起始相对简单。它对应于RNA聚合酶II（Pol II）掺入新生RNA分子的第一个核糖核苷酸。该核苷酸通过加帽得到保护并保留在成熟的信使RNA（mRNA）中。然而，在高等真核生物中，mRNA的末端与转录终止位点之间相隔数百到数千个碱基对。目前使用的基因组注释仅考虑成熟转录本的末端——前体mRNA切割发生的位点，而转录终止的区域未被注释。在此，我们描述了一种转录终止标记的证据，该证据可能在基因组研究中广泛适用。通过检测其C末端结构域苏氨酸4磷酸化的Pol II（Pol II CTD-T4ph），可以在全基因组范围内确定Pol II终止区域。处于这种状态的Pol II在离开DNA模板之前会暂停。到目前为止，这个有力的标记尚未得到充分利用，因为其在终止中的位置和作用的证据分散在多篇出版物中。我们总结了关于终止区域中Pol II CTD-T4ph的观察结果，并展示了生物信息学分析，进一步支持Pol II CTD-T4ph作为动物中的全局终止标记。
