Human RNase 7: a new cationic ribonuclease of the RNase A superfamily.
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.
Zhang
Jianzhi
J
Department of Ecology and Evolutionary Biology, University of Michigan, 3003 Natural Science Building, 830 North University Avenue, Ann Arbor, MI 48109, USA. jianzhi@umich.edu
Dyer
Kimberly D
KD
Rosenberg
Helene F
HF
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D012343:RNA, Transfer; D012260:Ribonucleases; C470000:Ribonuclease 7; D012259:Ribonuclease, Pancreatic