Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes
Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes
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DOI：
10.1038/s41598-019-49316-5
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发表时间：
2019-09-09
影响因子：
4.6
通讯作者：
Bhargava, Purnima
中科院分区：
文献类型：
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作者：
Bhalla, Pratibha;Shukla, Ashutosh;Bhargava, Purnima
RNA聚合酶（pol）III主要转录短的管家基因，产生稳定的非编码RNA。在体内由pol III高度转录的tRNA基因是已知的复制叉屏障。转录因子之一，PAF 1C（RNA聚合酶II相关因子1复合物）被报道与pol I和pol II相关并影响其转录。我们发现低水平的PAF 1C占用酵母pol III-转录基因，这是不相关的核小体位置，pol III占用和转录。PAF 1C与pol III转录复合物相互作用，并导致pol III在复制应激下从基因中丢失。遗传毒素暴露导致pol III而不是Paf 1基因丢失。相比之下，Paf 1缺失导致pol III、γ-H2 A和DNA pol 2以基因特异性方式占据增加。Paf 1通过影响pol III在基因上的暂停来限制pol III的积累，这降低了pol III对复制叉进展的屏障。
The RNA polymerase (pol) III transcribes mostly short, house-keeping genes, which produce stable, non-coding RNAs. The tRNAs genes, highly transcribed by pol III in vivo are known replication fork barriers. One of the transcription factors, the PAF1C (RNA polymerase II associated factor 1 complex) is reported to associate with pol I and pol II and influence their transcription. We found low level PAF1C occupancy on the yeast pol III-transcribed genes, which is not correlated with nucleosome positions, pol III occupancy and transcription. PAF1C interacts with the pol III transcription complex and causes pol III loss from the genes under replication stress. Genotoxin exposure causes pol III but not Paf1 loss from the genes. In comparison, Paf1 deletion leads to increased occupancy of pol III, gamma-H2A and DNA pol2 in gene-specific manner. Paf1 restricts the accumulation of pol III by influencing the pol III pause on the genes, which reduces the pol III barrier to the replication fork progression.