Baillat David, Hakimi Mohamed-Ali, Näär Anders M, Shilatifard Ali, Cooch Neil, Shiekhattar Ramin
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Cell. 2005 Oct 21;123(2):265-76. doi: 10.1016/j.cell.2005.08.019.
The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein-coding genes. A large body of data also implicates the CTD in the transcription and processing of RNAPII-mediated small nuclear RNAs (snRNAs). However, the identity of the complex (or complexes) that associates with the CTD and mediates the processing of snRNAs has remained elusive. Here, we describe an RNA polymerase II complex that contains at least 12 novel subunits, termed the Integrator, in addition to core RNAPII subunits. Two of the Integrator subunits display similarities to the subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit.
RNA聚合酶II（RNAPII）的C末端结构域（CTD）是蛋白质编码基因转录调控和RNA加工的重要组成部分。大量数据还表明CTD参与了RNAPII介导的小核RNA（snRNA）的转录和加工。然而，与CTD结合并介导snRNA加工的复合物（或多个复合物）的身份仍然难以捉摸。在这里，我们描述了一种RNA聚合酶II复合物，除了核心RNAPII亚基外，它还包含至少12个新的亚基，称为整合因子（Integrator）。整合因子的两个亚基与切割和聚腺苷酸化特异性因子（CPSF）复合物的亚基相似。我们表明，整合因子被招募到U1和U2 snRNA基因，并介导snRNA的3'末端加工。整合因子复合物在多细胞动物中是进化保守的，并且直接与RNA聚合酶II最大亚基的C末端结构域相互作用。
