The transcription factor Sfp1 imprints specific classes of mRNAs and links their synthesis and cytoplasmic decay

To function as a system, transcription and post-transcriptional stages must communicate - the underlying mechanism of which is still little studied. Here we focus on S. cerevisiae genes, transcription of which is regulated by Sfp1 that binds their promoters. We show that Sfp1 also binds downstream chromatin regions, thereby changing Pol II configuration, resulting in enhanced Pol II backtracking and possibly Rpb4 dissociation. Unexpectedly, this transcription factor binds >264 transcripts of these genes - near their 3’ ends – and regulates their deadenylation and stability. The interaction of Sfp1 with these mRNAs is controlled by the promoter and it occurs concomitantly with its dissociation from the chromatin. Collectively, we propose that Sfp1 accompanies Pol II and binds the RNA co-transcriptionally. It then accompanies these mRNAs to the cytoplasm and regulates their stability. Thus, Sfp1 co-transcriptional binding imprints the mRNA fate and serves as a paradigm for posttranscriptional regulation of specific mRNAs by the transcription apparatus.要实现系统层面的功能，转录与转录后阶段必须实现信号沟通——其背后的核心分子机制至今仍未得到充分研究。本文聚焦酿酒酵母（S. cerevisiae）基因，这类基因的转录过程受结合其启动子的Sfp1蛋白调控。我们发现，Sfp1还可结合下游染色质区域，由此改变RNA聚合酶II（Pol II）的构象，进而增强Pol II的回溯现象，并可能引发Rpb4亚基的解离。出乎意料的是，该转录因子还能结合这些基因的超过264种转录本，结合位点临近其3'端，并调控这些转录本的脱腺苷酸化过程与分子稳定性。Sfp1与这些mRNA的相互作用受启动子调控，且该过程与其从染色质上的解离同步发生。综上，我们提出如下模型：Sfp1会伴随Pol II完成共转录结合RNA的过程，随后伴随这些mRNA进入细胞质，并调控其稳定性。由此可见，Sfp1的共转录结合会印记mRNA的命运，并可作为转录装置调控特定mRNA转录后过程的经典研究范式。