Franks Tobias M, Benner Chris, Narvaiza Iñigo, Marchetto Maria C N, Young Janet M, Malik Harmit S, Gage Fred H, Hetzer Martin W
Laboratory of Molecular and Cellular Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA;
Genes Dev. 2016 May 15;30(10):1155-71. doi: 10.1101/gad.280941.116. Epub 2016 May 19.
Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear periphery and in the nucleoplasm in metazoans. Here we identify a widely expressed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for "soluble Pom121") that arose by genomic rearrangement before the divergence of hominoids. sPom121 lacks the nuclear membrane-anchoring domain and thus does not localize to the NPC. Instead, sPom121 colocalizes and interacts with nucleoplasmic Nup98, a previously identified transcriptional regulator, at gene promoters to control transcription of its target genes in human cells. Interestingly, sPom121 transcripts appear independently in several mammalian species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian evolution. Our findings implicate alternate transcription initiation as a mechanism to increase the functional diversity of NPC components.
核孔复合体（NPCs）在约15亿年前作为真核细胞中的核运输通道出现。虽然NPCs的主要作用是调节核质运输，但最近的研究表明，某些NPC蛋白在后生动物中还额外承担了影响核周和核质中基因表达的作用。在这里，我们鉴定出一种跨膜核孔蛋白（Nup）Pom121的广泛表达变体（命名为sPom121，即“可溶性Pom121”），它在类人猿分化之前通过基因组重排产生。sPom121缺乏核膜锚定结构域，因此不定位到NPC。相反，sPom121在基因启动子处与核质Nup98（一种先前鉴定的转录调节因子）共定位并相互作用，以控制其在人类细胞中靶基因的转录。有趣的是，sPom121转录本在几种哺乳动物物种中独立出现，这表明在哺乳动物进化过程中Nup介导的转录调节发生了趋同创新。我们的研究结果表明，交替转录起始是增加NPC组件功能多样性的一种机制。
