Centre for Cellular and Molecular Biology (Council of Scientific and Industrial Research), Hyderabad, India.
UT Southwestern Medical Center, Dallas, Texas, USA.
Sci Rep. 2019 Sep 9;9(1):12892. doi: 10.1038/s41598-019-49316-5.
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, γ-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.
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。tRNA 基因在体内由 pol III 高度转录,是已知的复制叉障碍。一种转录因子,PAF1C(RNA 聚合酶 II 相关因子 1 复合物)被报道与 pol I 和 pol II 结合,并影响它们的转录。我们发现酵母 pol III 转录基因上 PAF1C 的占有率较低,这与核小体位置、pol III 占有率和转录无关。PAF1C 与 pol III 转录复合物相互作用,导致复制应激下 pol III 从基因中丢失。遗传毒物暴露导致 pol III 而不是 Paf1 从基因中丢失。相比之下,Paf1 缺失导致 pol III、γ-H2A 和 DNA pol2 在基因特异性方式上的占有率增加。Paf1 通过影响 pol III 在基因上的暂停来限制 pol III 的积累,从而减少 pol III 对复制叉前进的障碍。