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 <i>Drosophila</i> 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 (snRNA) 基因的通用转录装置已得到广泛研究，但该过程中辅助激活因子的作用仍远未被完全阐明。本研究证实，果蝇 (Drosophila) 的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，并结合于由RNA聚合酶II (RNA polymerase II) 和RNA聚合酶III (RNA polymerase III，包括U6 snRNA) 转录的snRNA基因的启动子区域。研究显示，SAGA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，并结合于多个经Pol III转录的基因的启动子区域。敲除多个SAGA复合物亚基基因的突变会导致成年果蝇体内snRNA水平下降，表明SAGA确实是snRNA基因的转录辅助激活因子。所有经测试的SAGA复合物亚基突变均会降低经Pol II和Pol III转录的U型snRNA基因的转录水平。此外，SAGA复合物去泛素化模块与乙酰转移酶模块的突变同样会降低这类经Pol II和Pol III转录的U型snRNA基因的转录水平，这表明完整的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，这表明其广泛参与基因转录调控，进而维持细胞稳态。