Sheldon Kathryn E, Mauger David M, Arndt Karen M
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Mol Cell. 2005 Oct 28;20(2):225-36. doi: 10.1016/j.molcel.2005.08.026.
RNA synthesis and processing are coordinated by proteins that associate with RNA polymerase II (pol II) during transcription elongation. The yeast Paf1 complex interacts with RNA pol II and mediates histone modifications during elongation. To elucidate the functions of this complex, we isolated missense mutations in the gene encoding the Rtf1 subunit and used them to identify functionally interacting proteins. We identified NAB3 as a dosage suppressor of rtf1. Nab3, together with Nrd1, directs 3' end formation of nonpolyadenylated RNA pol II transcripts, such as snoRNAs. Deletion of Paf1, but not the Set1, Set2, or Dot1 histone methyltransferases, causes accumulation of snoRNA transcripts that are extended at their 3' ends. The Paf1 complex associates with and facilitates Nrd1 recruitment to the SNR47 gene, suggesting a direct involvement in 3' end formation. Our results reveal a posttranscriptional function for the Paf1 complex, which appears unrelated to its role in histone methylation.
RNA合成与加工过程由转录延伸过程中与RNA聚合酶II(pol II)相关联的蛋白质协调。酵母Paf1复合物在延伸过程中与RNA pol II相互作用并介导组蛋白修饰。为阐明该复合物的功能,我们分离了编码Rtf1亚基的基因中的错义突变,并利用它们来鉴定功能上相互作用的蛋白质。我们鉴定出NAB3是rtf1的剂量抑制因子。Nab3与Nrd1一起指导非聚腺苷酸化RNA pol II转录本(如snoRNA)的3'末端形成。缺失Paf1,而非Set1、Set2或Dot1组蛋白甲基转移酶,会导致snoRNA转录本在其3'末端延长并积累。Paf1复合物与Nrd1结合并促进其募集到SNR47基因,表明其直接参与3'末端形成。我们的结果揭示了Paf1复合物的转录后功能,这一功能似乎与其在组蛋白甲基化中的作用无关。