Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, 8000 Aarhus C, Denmark; Laboratory of Cellular and Structural Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, Building 1130, 8000 Aarhus C, Denmark.
Cell Rep. 2018 Jan 2;22(1):44-58. doi: 10.1016/j.celrep.2017.12.037.
Nuclear RNA metabolism is influenced by protein complexes connecting to both RNA-productive and -destructive pathways. The ZC3H18 protein binds the cap-binding complex (CBC), universally present on capped RNAs, while also associating with the nuclear exosome targeting (NEXT) complex, linking to RNA decay. To dissect ZC3H18 function, we conducted interaction screening and mutagenesis of the protein, which revealed a phosphorylation-dependent isoform. Surprisingly, the modified region of ZC3H18 associates with core histone proteins. Further examination of ZC3H18 function, by genome-wide analyses, demonstrated its impact on transcription of a subset of protein-coding genes. This activity requires the CBC-interacting domain of the protein, with some genes being also dependent on the NEXT- and/or histone-interacting domains. Our data shed light on the domain requirements of a protein positioned centrally in nuclear RNA metabolism, and they suggest that post-translational modification may modulate its function.
核 RNA 代谢受连接到 RNA 产生和破坏途径的蛋白质复合物的影响。ZC3H18 蛋白结合帽结合复合物 (CBC)，普遍存在于加帽的 RNA 上，同时还与核外切酶靶向 (NEXT) 复合物结合，连接到 RNA 降解。为了剖析 ZC3H18 的功能，我们对该蛋白进行了相互作用筛选和突变，揭示了一种依赖于磷酸化的同工型。令人惊讶的是，ZC3H18 的修饰区域与核心组蛋白蛋白结合。通过全基因组分析进一步研究 ZC3H18 的功能，表明其对一组蛋白质编码基因的转录有影响。这种活性需要该蛋白的 CBC 相互作用域，其中一些基因也依赖于 NEXT 和/或组蛋白相互作用域。我们的数据阐明了在核 RNA 代谢中处于中心位置的蛋白质的结构域要求，并表明翻译后修饰可能调节其功能。
