Simmons Heidi M, Ruis Brian L, Kapoor Meenal, Hudacek Andrew W, Conklin Kathleen F
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Gene. 2005 Feb 28;347(1):137-45. doi: 10.1016/j.gene.2004.12.027.
Proteins that contain the recently described MIF4G and/or MA3 domains function in translation, cell growth, proliferation, transformation, and apoptosis. Examples of MIF4G/MA3 containing proteins and their functions include eIF4G, which serves as a scaffold for assembly of factors required for translation initiation, programmed cell death protein 4 (Pdcd4) that inhibits translation and functions as a tumor suppressor, and NMD2, which is essential for nonsense-mediated mRNA decay. MIF4G and MA3 domains serve as binding sites for one or more isoforms of the eIF4A family of ATP-dependent DEAD-box RNA helicases that are required for translation and for nonsense-mediated decay. In this report, we describe the characterization of a novel MIF4G/MA3 family member called NOM1 (nucleolar protein with MIF4G domain 1) that was identified at the chromosome 7q36 breakpoint involved in 7;12 translocations associated with certain acute leukemias of childhood. NOM1, which includes a previously described EST called c7orf3, encodes a ubiquitously expressed transcript composed of 11 exons and an approximately 3 kb 3' UTR that contains several Alu repeats. The predicted NOM1 protein contains one MIF4G domain and one MA3 domain and, consistent with data obtained with other MIF4G/MA3 proteins, interacts with members of the eIF4A family of helicases. Database searches reveal that NOM1 homologs exist in several organisms and that at least two of these are essential genes. Finally, like its Saccharomyces cerevisiae homolog Sgd1p, NOM1 localizes predominantly to the nucleolus. These data demonstrate that NOM1 is a new member of the MIF4G/MA3 family of proteins and suggest that it may provide an essential function in metazoans.
含有最近描述的MIF4G和/或MA3结构域的蛋白质在翻译、细胞生长、增殖、转化和细胞凋亡中发挥作用。含有MIF4G/MA3的蛋白质及其功能的例子包括：真核生物翻译起始因子4G（eIF4G），它作为翻译起始所需因子组装的支架；程序性细胞死亡蛋白4（Pdcd4），它抑制翻译并作为肿瘤抑制因子发挥作用；以及NMD2，它对无义介导的mRNA降解至关重要。MIF4G和MA3结构域作为ATP依赖的DEAD盒RNA解旋酶eIF4A家族一种或多种亚型的结合位点，这些亚型是翻译和无义介导的降解所必需的。在本报告中，我们描述了一种名为NOM1（含MIF4G结构域1的核仁蛋白）的新型MIF4G/MA3家族成员的特征，它是在与儿童某些急性白血病相关的7；12易位所涉及的7号染色体q36断点处鉴定出来的。NOM1，其中包括一个先前描述的名为c7orf3的EST，编码一个由11个外显子和一个约3 kb的3'非翻译区（UTR）组成的普遍表达的转录本，该非翻译区包含几个Alu重复序列。预测的NOM1蛋白包含一个MIF4G结构域和一个MA3结构域，并且与其他MIF4G/MA3蛋白获得的数据一致，它与解旋酶eIF4A家族的成员相互作用。数据库搜索显示，NOM1同源物存在于几种生物中，并且其中至少两个是必需基因。最后，与其酿酒酵母同源物Sgd1p一样，NOM1主要定位于核仁。这些数据表明NOM1是MIF4G/MA3蛋白质家族的一个新成员，并表明它可能在多细胞动物中发挥重要功能。
