Park Sung Hee, Nguyen Tu N, Kirkham Justin K, Lee Ju Huck, Günzl Arthur
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030-6403, USA.
Mol Biochem Parasitol. 2011 Nov;180(1):35-42. doi: 10.1016/j.molbiopara.2011.06.008. Epub 2011 Jul 23.
Trypanosoma brucei has a multifunctional RNA polymerase (pol) I that transcribes ribosomal gene units (RRNA) and units encoding its major cell surface proteins variant surface glycoprotein (VSG) and procyclin. Previous analysis of tandem affinity-purified, transcriptionally active RNA pol I identified ten subunits including an apparently trypanosomatid-specific protein termed RPA31. Another ortholog was identified in silico. No orthologs of the yeast subunit doublet RPA43/RPA14 have been identified yet. Instead, a recent report presented evidence that RPB7, the RNA pol II paralog of RPA43, is an RNA pol I subunit and essential for RRNA and VSG transcription in bloodstream form trypanosomes [18]. Revisiting this attractive hypothesis, we were unable to detect a stable interaction between RPB7 and RNA pol I in either reciprocal co-immunoprecipitation or tandem affinity purification. Furthermore, immunodepletion of RPB7 from extract virtually abolished RNA pol II transcription in vitro but had no effect on RRNA or VSG ES promoter transcription in the same reactions. Accordingly, chromatin immunoprecipitation analysis revealed cross-linking of RPB7 to known RNA pol II transcription units but not to the VSG ES promoter or to the 18S rRNA coding region. Interestingly, RPB7 did crosslink to the RRNA promoter but so did the RNA pol II-specific subunit RPB9 suggesting that RNA pol II is recruited to this promoter. Overall, our data led to the conclusion that RNA pol I transcription in T. brucei does not require the RNA pol II subunit RPB7.
布氏锥虫具有一种多功能的RNA聚合酶(pol)I,它转录核糖体基因单元(rRNA)以及编码其主要细胞表面蛋白即变异表面糖蛋白(VSG)和前环素的单元。先前对串联亲和纯化的转录活性RNA pol I进行的分析鉴定出了十个亚基,其中包括一种明显为锥虫特异性的蛋白质,称为RPA31。通过计算机分析鉴定出了另一个直系同源物。尚未鉴定出酵母亚基双重体RPA43/RPA14的直系同源物。相反,最近的一份报告提出证据表明,RPA43的RNA pol II旁系同源物RPB7是RNA pol I的一个亚基,并且对于血流形式锥虫中的rRNA和VSG转录至关重要[18]。重新审视这个引人关注的假设时,我们在相互免疫共沉淀或串联亲和纯化中均未能检测到RPB7与RNA pol I之间的稳定相互作用。此外,从提取物中免疫去除RPB7实际上消除了体外的RNA pol II转录,但对相同反应中的rRNA或VSG ES启动子转录没有影响。因此,染色质免疫沉淀分析显示RPB7与已知的RNA pol II转录单元发生交联,但与VSG ES启动子或18S rRNA编码区域没有交联。有趣的是,RPB7确实与rRNA启动子发生了交联,但RNA pol II特异性亚基RPB9也如此,这表明RNA pol II被招募到了这个启动子上。总体而言,我们的数据得出结论,布氏锥虫中的RNA pol I转录不需要RNA pol II亚基RPB7。