近日，英国弗朗西斯·克里克研究所Jesper Q. Svejstrup课题组合作发现了两个抗mRNA转录终止的蛋白：SCAF4和SCAF8。2019年6月出版的《细胞》杂志发表了这项研究成果。

正确的基因表达需要精确调控mRNA的转录终止。在这项工作中，研究人员阐述了SCAF4与SCAF8两个蛋白作为抗转录终止的角色，它们能够抑制对上游可变polyA位点的利用。SCAF4/8蛋白能够在上游可变polyA位点处与超磷酸化的RNA聚合酶II CTD结构域结合。同时敲除人源的SCAF4和SCAF8会导致polyA位点选择的改变与转录提前终止，进而使得mRNA截短、蛋白质缺失功能性结构域，最后引起细胞死亡。

此外，尽管SCAF4和SCAF8在抑制mRNA提前终止方面的功能是冗余的，但它们也具有各自独立的、非必需的功能。SCAF8是一个RNA聚合酶II的转录延伸因子，而SCAF4在SCAF8存在的情况下，调控在经典的远端转录终止位点进行正确的转录终止。SCAF4和SCAF8共同协调了转录延伸到转录终止的转换，以确保人体细胞中正确的polyA位点选择与RNA聚合酶II的转录终止。

附：英文原文

Title: SCAF4 and SCAF8, mRNA Anti-Terminator Proteins

Author: Lea H. Gregersen, Richard Mitter, Alejandro P. Ugalde, Takayuki Nojima, Nicholas J. Proudfoot, Reuven Agami, Aengus Stewart, Jesper Q. Svejstrup

Issue&Volume: Jun 13, 2019 Volume 177Issue 7 

Abstract: Accurate regulation of mRNA termination is required for correct gene expression. Here, we describe a role for SCAF4 and SCAF8 as anti-terminators, suppressing the use of early, alternative polyadenylation (polyA) sites. The SCAF4/8 proteins bind the hyper-phosphorylated RNAPII C-terminal repeat domain (CTD) phosphorylated on both Ser2 and Ser5 and are detected at early, alternative polyA sites. Concomitant knockout of human SCAF4 and SCAF8 results in altered polyA selection and subsequent early termination, leading to expression of truncated mRNAs and proteins lacking functional domains and is cell lethal. While SCAF4 and SCAF8 work redundantly to suppress early mRNA termination, they also have independent, non-essential functions. SCAF8 is an RNAPII elongation factor, whereas SCAF4 is required for correct termination at canonical, distal transcription termination sites in the presence of SCAF8. Together, SCAF4 and SCAF8 coordinate the transition between elongation and termination, ensuring correct polyA site selection and RNAPII transcriptional termination in human cells.

DOI: https://doi.org/10.1016/j.cell.2019.04.038

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30457-X