The role of SAGA coactivator complex in snRNA transcription

The general snRNA gene transcription apparatus has been extensively studied. However, the role of coactivators in this process is far from being clearly understood. Here, we have demonstrated that the Drosophila SAGA complex interacts with the PBP complex, the key component of the snRNA gene transcription apparatus, and is present at the promoter regions of the snRNA genes transcribed by both the RNA polymerase II and RNA polymerase III (U6 snRNA). We show that SAGA interacts with the Brf1 transcription factor, which is a part of the RNA polymerase III transcription apparatus and is present at promoters of a number of Pol III-transcribed genes. Mutations inactivating several SAGA subunit genes resulted in reduced snRNA levels in adult flies, indicating that SAGA is indeed the transcriptional coactivator for the snRNA genes. The transcription of the Pol II and Pol III-transcribed U genes was reduced by mutations in all tested SAGA complex subunits. Therefore, the transcription of the Pol II and Pol III-transcribed U genes was reduced by the mutations in the deubiquitinase module, as well as in the acetyltransferase module of the SAGA, indicating that the whole complex is essential for their transcription. Therefore, the SAGA complex activates snRNA genes suggesting its wide involvement in the regulation of gene transcription, and consequently, in the maintenance of cellular homeostasis.

小核RNA（small nuclear RNA，snRNA）基因的通用转录装置已得到广泛研究，但共激活因子在此过程中的作用仍远未明确。本研究证实，果蝇SAGA复合物可与snRNA基因转录装置的核心组分PBP复合物相互作用，且该复合物富集于由RNA聚合酶II（Pol II）和RNA聚合酶III（Pol III）转录的snRNA基因（含U6 snRNA）的启动子区域。研究表明，SAGA复合物可与属于RNA聚合酶III转录装置组分的Brf1转录因子相互作用，并结合于多个Pol III转录基因的启动子区域。失活多个SAGA亚基基因的突变会导致成虫体内snRNA水平显著降低，这表明SAGA确实是snRNA基因的转录共激活因子。针对所有检测过的SAGA复合物亚基的突变，均可降低Pol II和Pol III转录的U类snRNA基因的转录水平。进一步研究发现，SAGA复合物的去泛素化模块与乙酰转移酶模块发生突变后，同样会降低Pol II和Pol III转录的U类snRNA基因的转录活性，这说明完整的SAGA复合物对这类基因的转录至关重要。综上，SAGA复合物可激活snRNA基因的表达，这提示其广泛参与基因转录调控，进而在维持细胞稳态过程中发挥关键作用。