Ahuja Richa, Kumar Vijay
Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
FEBS J. 2017 Jul;284(13):2066-2077. doi: 10.1111/febs.14104. Epub 2017 May 29.
RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription. Our chromatin immunoprecipitation studies suggested that endogenous AP-1 factors bind to their cognate promoter elements during the G1/S transition of cell cycle apparently synchronous with Pol III transcriptional activity. Furthermore, the interaction of c-Jun with histone acetyltransferase p300 promoted the recruitment of p300/CBP complex on the promoters and facilitated the occupancy of Pol III transcriptional machinery via histone acetylation and chromatin remodeling. The findings of our study, together, suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation.
RNA聚合酶III转录结构多样的一组必需非编码RNA,包括5S核糖体RNA(5SrRNA)和U6小核RNA(U6 snRNA)。这些非编码RNA参与RNA加工和核糖体生物合成,因此将Pol III的活性与蛋白质合成、细胞生长和增殖速率联系起来。尽管已有报道一些与Pol II相关的转录因子参与Pol III依赖性转录,但其被激活蛋白1(AP-1)因子c-Fos和c-Jun激活的情况仍未得到探索。在此,我们表明c-Fos和c-Jun结合到5S rRNA(I型)和U6 snRNA(III型)基因启动子调控区域的特定位点并刺激它们的转录。我们的染色质免疫沉淀研究表明,内源性AP-1因子在细胞周期的G1/S期与它们的同源启动子元件结合,这显然与Pol III转录活性同步。此外,c-Jun与组蛋白乙酰转移酶p300的相互作用促进了p300/CBP复合物在启动子上的募集,并通过组蛋白乙酰化和染色质重塑促进了Pol III转录机制的占据。我们的研究结果共同表明,AP-1因子是Pol III驱动的5S rRNA和U6 snRNA表达的新型调节因子,在细胞增殖中具有潜在作用。