Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, Rochester, NY 14642, USA.
Biochem Biophys Res Commun. 2010 Feb 26;393(1):106-10. doi: 10.1016/j.bbrc.2010.01.093. Epub 2010 Jan 29.
UAP56, an ATP dependent RNA helicase that also has ATPase activity, is a DExD/H box protein that is phylogenetically grouped with the eukaryotic initiation factor eIF4A, the prototypical member of the DExD/H box family of helicases. UAP56, also known as BAT1, is an essential RNA splicing factor required for spliceosome assembly and mRNA export but its role in protein synthesis is not known. Here we demonstrate that UAP56 regulates protein synthesis and growth in cardiomyocytes. We found that wild-type (WT) UAP56 increased serum induced protein synthesis in HeLa cells. UAP56 mutants lacking ATPase and/or helicase activity inhibited protein synthesis compared with WT UAP56, suggesting that the ATPase and RNA helicase activity of UAP56 is important for protein synthesis. UAP56 siRNA inhibited phenylephrine (PE) induced protein synthesis in cardiomyocytes and inhibited PE induced cardiomyocyte hypertrophy. Our data demonstrate that UAP56 is an important regulator of protein synthesis and plays an important role in the regulation of cardiomyocyte growth.
UAP56 是一种依赖于 ATP 的 RNA 解旋酶，也具有 ATPase 活性，它是一种 DExD/H 盒蛋白，与真核起始因子 eIF4A 具有系统发育关系，eIF4A 是 DExD/H 盒家族解旋酶的原型成员。UAP56 也称为 BAT1，是剪接体组装和 mRNA 输出所必需的必需 RNA 剪接因子，但它在蛋白质合成中的作用尚不清楚。在这里，我们证明 UAP56 可调节心肌细胞中的蛋白质合成和生长。我们发现，野生型（WT）UAP56 增加了 HeLa 细胞中血清诱导的蛋白质合成。与 WT UAP56 相比，缺乏 ATPase 和/或解旋酶活性的 UAP56 突变体抑制了蛋白质合成，这表明 UAP56 的 ATPase 和 RNA 解旋酶活性对于蛋白质合成很重要。UAP56 siRNA 抑制了去甲肾上腺素（PE）诱导的心肌细胞中的蛋白质合成，并抑制了 PE 诱导的心肌细胞肥大。我们的数据表明，UAP56 是蛋白质合成的重要调节剂，在调节心肌细胞生长中起重要作用。
