El Hage Aziz, Webb Shaun, Kerr Alastair, Tollervey David
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
PLoS Genet. 2014 Oct 30;10(10):e1004716. doi: 10.1371/journal.pgen.1004716. eCollection 2014 Oct.
During transcription, the nascent RNA can invade the DNA template, forming extended RNA-DNA duplexes (R-loops). Here we employ ChIP-seq in strains expressing or lacking RNase H to map targets of RNase H activity throughout the budding yeast genome. In wild-type strains, R-loops were readily detected over the 35S rDNA region, transcribed by Pol I, and over the 5S rDNA, transcribed by Pol III. In strains lacking RNase H activity, R-loops were elevated over other Pol III genes, notably tRNAs, SCR1 and U6 snRNA, and were also associated with the cDNAs of endogenous TY1 retrotransposons, which showed increased rates of mobility to the 5'-flanking regions of tRNA genes. Unexpectedly, R-loops were also associated with mitochondrial genes in the absence of RNase H1, but not of RNase H2. Finally, R-loops were detected on actively transcribed protein-coding genes in the wild-type, particularly over the second exon of spliced ribosomal protein genes.
在转录过程中,新生RNA可侵入DNA模板,形成延伸的RNA-DNA双链体(R环)。在此,我们在表达或缺乏核糖核酸酶H的菌株中采用染色质免疫沉淀测序(ChIP-seq)技术,以绘制整个芽殖酵母基因组中核糖核酸酶H活性的靶点。在野生型菌株中,在由RNA聚合酶I转录的35S核糖体DNA区域以及由RNA聚合酶III转录的5S核糖体DNA上很容易检测到R环。在缺乏核糖核酸酶H活性的菌株中,R环在其他RNA聚合酶III基因(特别是tRNA、SCR1和U6小核RNA)上有所增加,并且还与内源性TY1逆转录转座子的cDNA相关,这些逆转录转座子向tRNA基因的5'侧翼区域的移动速率增加。出乎意料的是,在缺乏核糖核酸酶H1而非核糖核酸酶H2的情况下,R环也与线粒体基因相关。最后,在野生型的活跃转录的蛋白质编码基因上检测到R环,特别是在剪接的核糖体蛋白基因的第二个外显子上。