Lemay Jean-François, Marguerat Samuel, Larochelle Marc, Liu Xiaochuan, van Nues Rob, Hunyadkürti Judit, Hoque Mainul, Tian Bin, Granneman Sander, Bähler Jürg, Bachand François
RNA Group, Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada;
MRC Clinical Sciences Centre (CSC), London W12 0NN, United Kingdom; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom;
Genes Dev. 2016 Jul 1;30(13):1558-72. doi: 10.1101/gad.280222.116.
Termination of RNA polymerase II (RNAPII) transcription is associated with RNA 3' end formation. For coding genes, termination is initiated by the cleavage/polyadenylation machinery. In contrast, a majority of noncoding transcription events in Saccharomyces cerevisiae does not rely on RNA cleavage for termination but instead terminates via a pathway that requires the Nrd1-Nab3-Sen1 (NNS) complex. Here we show that the Schizosaccharomyces pombe ortholog of Nrd1, Seb1, does not function in NNS-like termination but promotes polyadenylation site selection of coding and noncoding genes. We found that Seb1 associates with 3' end processing factors, is enriched at the 3' end of genes, and binds RNA motifs downstream from cleavage sites. Importantly, a deficiency in Seb1 resulted in widespread changes in 3' untranslated region (UTR) length as a consequence of increased alternative polyadenylation. Given that Seb1 levels affected the recruitment of conserved 3' end processing factors, our findings indicate that the conserved RNA-binding protein Seb1 cotranscriptionally controls alternative polyadenylation.
RNA聚合酶II(RNAPII)转录的终止与RNA 3'末端的形成相关。对于编码基因,终止由切割/聚腺苷酸化机制启动。相比之下,酿酒酵母中的大多数非编码转录事件并不依赖RNA切割来终止,而是通过一种需要Nrd1-Nab3-Sen1(NNS)复合物的途径终止。在这里,我们表明粟酒裂殖酵母中Nrd1的直系同源物Seb1在类似NNS的终止过程中不起作用,而是促进编码和非编码基因的聚腺苷酸化位点选择。我们发现Seb1与3'末端加工因子相关联,在基因的3'末端富集,并结合切割位点下游的RNA基序。重要的是,Seb1的缺陷导致由于可变聚腺苷酸化增加而导致3'非翻译区(UTR)长度广泛变化。鉴于Seb1水平影响保守的3'末端加工因子的募集,我们的发现表明保守的RNA结合蛋白Seb1在转录过程中控制可变聚腺苷酸化。