A posttranscriptional role for the yeast Paf1-RNA polymerase II complex is revealed by identification of primary targets
A posttranscriptional role for the yeast Paf1-RNA polymerase II complex is revealed by identification of primary targets
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DOI：
10.1016/j.molcel.2005.08.023
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发表时间：
2005-10-28
期刊：
影响因子：
16
通讯作者：
Jaehning, JA
中科院分区：
文献类型：
--
作者：
Penheiter, KL;Washburn, TM;Jaehning, JA
酵母Paf1复合体(Paf1C：Paf1、CDc73、Ctr9、Rtf1和Leo1)与RNA聚合酶II(Pol II)在转录活性基因的启动子和编码区相关，但只有一小部分基因的转录丰度因Paf1的缺失而改变。通过使用PAF1和微阵列的条件等位基因和零等位基因，我们确定了Paf1C的主要和次要靶点的身份。初级和次级Paf1C靶基因启动子对Paf1缺失均无反应。相反，Paf1缺失改变了主要靶基因SDA1和MAK21的Poly(A)位点的利用，导致3‘-延伸mRNAs的丰度增加。3‘-延伸的MAK21 RNA对无意义介导的衰退(NMD)很敏感，这表明在没有UPF1的情况下，它的丰度增加。因此，尽管Paf1C在起始和延伸过程中与Pol II相关，但这些依赖于Paf1的转录本丰度的关键变化是由于转录后加工的变化。
The yeast Paf1 complex (Paf1C: Paf1, Cdc73, Ctr9, Rtf1, and Leo1) is associated with RNA Polymerase II (Pol II) at promoters and coding regions of transcriptionally active genes, but transcript abundance for only a small subset of genes is altered by loss of Paf1. By using conditional and null alleles of PAF1 and microarrays, we determined the identity of both primary and secondary targets of the Paf1C. Neither primary nor secondary Paf1C target promoters were responsive to loss of Paf1. Instead, Paf1 loss altered poly(A) site utilization of primary target genes SDA1 and MAK21, resulting in increased abundance of 3'-extended mRNAs. The 3'-extended MAK21 RNA is sensitive to nonsense-mediated decay (NMD), as revealed by its increased abundance in the absence of Upf1. Therefore, although the Paf1C is associated with Pol II at initiation and during elongation, these critical Paf1-dependent changes in transcript abundance are due to alterations in posttranscriptional processing.