Yang Fan, Hsu Peter, Lee Susan D, Yang Wen, Hoskinson Derick, Xu Weihao, Moore Claire, Varani Gabriele
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
RNA. 2017 Jan;23(1):98-107. doi: 10.1261/rna.058354.116. Epub 2016 Oct 25.
3'-End processing of pre-mRNAs prior to packaging and export to the cytoplasm of the mature transcript is a highly regulated process executed by several tens of protein factors that recognize poorly conserved RNA signals. Among them is Pcf11, a highly conserved, multidomain protein that links transcriptional elongation, 3'-end processing, and transcription termination. Here we report the structure and biochemical function of Pcf11's C-terminal domain, which is conserved from yeast to humans. We identify a novel zinc-finger fold, resembling a trillium flower. Structural, biochemical, and genetic analyses reveal a highly conserved surface that plays a critical role in both cleavage and polyadenylation. These findings provide further insight into this important protein and its multiple functional roles during cotranscriptional RNA processing.
在将前体mRNA进行包装并输出到成熟转录本的细胞质之前，对其3'末端进行加工是一个受到高度调控的过程，由几十种识别保守性较差的RNA信号的蛋白质因子执行。其中包括Pcf11，它是一种高度保守的多结构域蛋白质，连接转录延伸、3'末端加工和转录终止。在此，我们报告了Pcf11 C末端结构域的结构和生化功能，该结构域在从酵母到人类中都是保守的。我们鉴定出一种类似延龄草花的新型锌指结构。结构、生化和遗传分析揭示了一个在切割和聚腺苷酸化中都起关键作用的高度保守表面。这些发现为深入了解这种重要蛋白质及其在共转录RNA加工过程中的多种功能作用提供了进一步的见解。
