Common mechanism of transcription termination at coding and noncoding RNA genes in fission yeast

Termination of RNA polymerase II (RNAPII) transcription is a fundamental step of gene expression that is critical for determining the borders between genes. In budding yeast, termination at protein-coding genes is initiated by the cleavage/polyadenylation machinery, whereas termination of most noncoding RNA (ncRNA) genes occurs via the Nrd1-Nab3-Sen1 (NNS) pathway. Unexpectedly, we show here that NNS-like transcription termination is not conserved in fission yeast. Instead, genome-wide location analyses show global recruitment of mRNA 3’ end processing factors at the end of ncRNA genes, including snoRNAs and snRNAs, and that this recruitment coincides with high levels of Ser2 and Tyr1 phosphorylation on the RNAPII C-terminal domain. We further show that termination of mRNA and ncRNA transcription requires the conserved Ysh1/CPSF-73 and Dhp1/XRN2 nucleases, supporting widespread cleavage-dependent transcription termination in fission yeast. Our findings thus reveal that a common mode of transcription termination can produce functionally and structurally distinct types of polyadenylated and non-polyadenylated RNAs.RNA聚合酶II（RNA polymerase II, RNAPII）的转录终止是基因表达的核心基础步骤，对界定基因间边界具有关键作用。在出芽酵母（budding yeast）中，蛋白编码基因的转录终止由剪切-多聚腺苷酸化复合体启动；而大多数非编码RNA（noncoding RNA, ncRNA）基因的转录终止则通过Nrd1-Nab3-Sen1（NNS）通路完成。令人意外的是，本研究发现类NNS转录终止通路在裂殖酵母（fission yeast）中并不保守。全基因组定位分析显示，包括小核仁RNA（small nucleolar RNA, snoRNAs）与小核RNA（small nuclear RNA, snRNAs）在内的ncRNA基因末端，会发生mRNA 3'端加工因子的全局性招募，且该招募现象与RNA聚合酶II C端结构域上高水平的Ser2和Tyr1磷酸化相吻合。本研究进一步证实，mRNA与ncRNA的转录终止均需要保守的Ysh1/CPSF-73和Dhp1/XRN2核酸酶，这为裂殖酵母中广泛存在依赖剪切的转录终止机制提供了实验支撑。综上，本研究结果表明，一种常见的转录终止模式可产生功能与结构均存在显著差异的多聚腺苷酸化与非多聚腺苷酸化RNA。