Paf1 Has Distinct Roles in Transcription Elongation and Differential Transcript Fate.
Paf1 Has Distinct Roles in Transcription Elongation and Differential Transcript Fate.
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DOI：
10.1016/j.molcel.2017.01.006
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发表时间：
2017-02-16
期刊：
影响因子：
16
通讯作者：
Mellor J
中科院分区：
文献类型：
--
作者：
Fischl H;Howe FS;Furger A;Mellor J
RNA聚合酶II（Pol 2）通过染色质的运动和新生转录物的共转录加工和命运由转录延伸因子（TEF）如聚合酶相关因子1（Paf 1）协调，但目前尚不清楚TEF是否具有基因特异性功能。使用链特异性核苷酸解析技术，我们发现Pol 2上的Paf 1水平在基因之间变化，通过启动子由环境因素动态控制，并反映编码转录物上的加工和出口因素的水平。Pol 2上高水平的Paf 1促进转录核输出，而低水平反映核保留。缺乏Paf 1的菌株显示出明显的延伸缺陷，尽管Pol 2上低水平的Paf 1足以进行转录延伸。我们的研究结果支持不同的Paf 1功能：一个核心的一般功能，在转录延伸，满足最低的Paf 1水平，并在确定差异转录命运的调节功能，通过改变Paf 1的Pol 2水平。使用TEF-seq的Pol 2上Paf 1的链特异性图谱Paf 1影响所有基因的转录延伸Paf 1在Pol 2上动态富集/耗尽，与其在延伸中的作用无关Paf 1富集促进编码转录物的核输出Fischl et al.显示不同的基因被与不同水平的延伸因子Paf 1相关的RNA聚合酶转录。Paf 1水平影响转录物是否保留在细胞核中或输出到细胞质中，这一功能与Paf 1在转录延伸中的作用不同。
RNA polymerase II (Pol2) movement through chromatin and the co-transcriptional processing and fate of nascent transcripts is coordinated by transcription elongation factors (TEFs) such as polymerase-associated factor 1 (Paf1), but it is not known whether TEFs have gene-specific functions. Using strand-specific nucleotide resolution techniques, we show that levels of Paf1 on Pol2 vary between genes, are controlled dynamically by environmental factors via promoters, and reflect levels of processing and export factors on the encoded transcript. High levels of Paf1 on Pol2 promote transcript nuclear export, whereas low levels reflect nuclear retention. Strains lacking Paf1 show marked elongation defects, although low levels of Paf1 on Pol2 are sufficient for transcription elongation. Our findings support distinct Paf1 functions: a core general function in transcription elongation, satisfied by the lowest Paf1 levels, and a regulatory function in determining differential transcript fate by varying the level of Paf1 on Pol2. Strand-specific maps of Paf1 on Pol2 using TEF-seq Paf1 influences transcription elongation at all genes Paf1 is dynamically enriched/depleted on Pol2, independent of its role in elongation Paf1 enrichment promotes nuclear export of the encoded transcripts Fischl et al. show that different genes are transcribed by RNA polymerase associated with different levels of the elongation factor Paf1. Paf1 levels influence whether transcripts are retained in the nucleus or exported to the cytoplasm, a function distinct from Paf1’s role in transcription elongation.