Zhang Jianzhi, Dyer Kimberly D, Rosenberg Helene F
Department of Ecology and Evolutionary Biology, University of Michigan, 3003 Natural Science Building, 830 North University Avenue, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2003 Jan 15;31(2):602-7. doi: 10.1093/nar/gkg157.
Here we report on the expression and function of RNase 7, one of the final RNase A superfamily ribonucleases identified in the human genome sequence. The human RNase 7 gene is expressed in various somatic tissues including the liver, kidney, skeletal muscle and heart. Recombinant RNase 7 is ribonucleolytically active against yeast tRNA, as expected from the presence of eight conserved cysteines and the catalytic histidine-lysine- histidine triad which are signature motifs of this superfamily. The protein is atypically cationic with an isoelectric point (pI) of 10.5. Expression of recombinant RNase 7 in Escherichia coli completely inhibits the growth of the host bacteria, similar to what has been observed for the cationic RNase, eosinophil cationic protein (ECP/RNase 3, pI 11.4). An in vitro assay demonstrates dose-dependent cytotoxicity of RNase 7 against bacteria E.coli, Pseudomonas aeruginosa and Staphylococcus aureus. While RNase 7 and ECP/RNase 3 are both cationic and share this particular aspect of functional similarity, their protein sequence identity is only 40%. Of particular interest, ECP/RNase 3's cationicity is based on an (over)abundance of arginine residues, whereas RNase 7 includes an excess of lysine. This difference, in conjunction with the independent origins and different expression patterns, suggests that RNase 7 and ECP/RNase 3 may have been recruited to target different pathogens in vivo, if their physiological functions are indeed host defenses.
在此，我们报告核糖核酸酶7（RNase 7）的表达与功能，它是人类基因组序列中确定的最后一个核糖核酸酶A超家族核糖核酸酶。人类RNase 7基因在包括肝脏、肾脏、骨骼肌和心脏在内的各种体细胞组织中表达。重组RNase 7对酵母tRNA具有核糖核酸酶活性，正如从八个保守半胱氨酸以及催化性组氨酸-赖氨酸-组氨酸三联体的存在所预期的那样，这些是该超家族的标志性基序。该蛋白是非典型阳离子性的，其等电点（pI）为10.5。重组RNase 7在大肠杆菌中的表达完全抑制宿主细菌的生长，这与阳离子核糖核酸酶嗜酸性粒细胞阳离子蛋白（ECP/RNase 3，pI 11.4）的情况类似。体外试验表明RNase 7对大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌具有剂量依赖性细胞毒性。虽然RNase 7和ECP/RNase 3都是阳离子性的，并且在功能上有这一特殊的相似之处，但它们的蛋白质序列同一性仅为40%。特别有趣的是，ECP/RNase 3的阳离子性基于精氨酸残基的（过）量，而RNase 7则含有过量的赖氨酸。这种差异，连同独立的起源和不同的表达模式，表明如果RNase 7和ECP/RNase 3的生理功能确实是宿主防御功能，那么它们可能在体内被招募来靶向不同的病原体。
