written by: bjlbyron•edited by: Emma Lloyd•updated: 9/16/2010
The ribonuclease-1 gene is involved in many important processes in our bodies. This article describes this interesting gene, what it does in the human body, and the ribonuclease-1 gene mutations and the genetic studies that have helped biologists characterize its molecular function.
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What Is Ribonuclease-1 And What Does It Do?
The human ribonuclease-1 gene, which is often abbreviated hRNase-1, encodes a small protein consisting of 156 amino acid molecules that participates in the breakdown of the ribonucleic acid (RNA) that we ingest in the foods we eat and in the inactivation of the Human Immunodeficiency Virus (HIV), among its other functions.
The hRNase-1 gene is expressed at elevated levels both in the pancreas and in endothelial cells. hRNase-1 protein produced in the pancreas is excreted into the duodenum and hRNAse-1 protein synthesized in endothelial cells is excreted into blood plasma. This protein also is expressed in other tissues, although not as strongly as it is in the pancreas and in endothelial cells. These other tissues include the brain, testis, ovaries and mammary gland. In addition to blood plasma, hRNase-1 protein is found in urine, saliva and breast milk.
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hRNase-1 Gene Mutations
Only two naturally-occurring DNA sequence variants of the hRNase-1 gene are known to exist, each one of which is a single nucleotide polymorphism (SNP). One SNP is designated rs11545379 and the other is designated rs1804215, and each one of these SNPs is a guanine-to-thymine, or "G-to-T", nucleic acid base substitution. That is, while most humans have a guanine residue in two particular positions of the hRNase-1 gene sequence, it has been determined that some individuals have a thymine residue, and not a guanine residue, at one of those positions.
In the case of SNP rs11545379, the G-to-T mutation causes an asparagine amino acid residue to be synthesized in the hRNAse-1 protein in the position at which a lysine amino acid residue appears in most individuals (specifically, this is at amino acid position 130 of the protein sequence).
In the case of SNP rs1804215, the G-to-T mutation causes a leucine amino acid residue to be synthesized in the hRNAse-1 protein in the position at which an arginine amino acid residue appears in most individuals (specifically, this is at amino acid position 67 of the protein sequence). Interestingly, neither one of these SNPs appears to have any significant effect on the well-being of individuals who harbor them in their genome.
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Although the two known naturally-occurring SNPs do not appear to confer any observable consequences to the people who have them, biologists have learned much about the molecular function of the hRNase-1 gene and its encoded protein through various molecular genetic studies.
For example, one of these studies has shown that the first 28 amino acid residues of the hRNase-1 protein serve as a signal peptide, which is a protein sequence that directs the transport of a protein to specific locations within and outside of the cells in which that protein is synthesized. Further, it is known that each one of the asparagine amino acid residues at positions 62, 104 and 116 of the hRNase-1 protein are necessary for glycosylation to occur (glycosylation is a cellular process that is needed for proper protein folding and preservation of protein integrity, among other things).
Finally, it is known that the asparagine and glycine amino acid residues at positions 116 and 117, respectively, of the hRNase-1 protein are not critical to inhibition of the protein by RNase1 inhibitor 1, which is an enzyme that blocks the activity of the hRNase-1 protein by binding to it. That is, when an arginine residue and a serine residue, respectively, are substituted for the asparagine and glycine amino acid residues at positions 116 and 117, RNase1 inhibitor 1 is still able to bind to hRNase1 to effectively block its activity.
While a fair amount in known about hRNAse-1, there is much more left to learn. Fortunately, several groups of scientists are actively studying this gene. Identification of additional ribonuclease-1 gene mutations in the general population and further molecular genetic studies should help facilitate the goal of better understanding the function of this interesting and important gene.
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J.J. Beintema et al., The amino acid sequence of human pancreatic ribonuclease, Anal. Biochem., 136:48-64 (1984).
J. Pous et al., Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases, Journal of Molecular Biology, 303:49-60 (2000).
M. Ueki et al., Development of genotyping methods for single nucleotide polymorphism in the human pancreatic ribonuclease gene (RNASE1) and their application to population studies, Biochemical Genetics, 46:145-53 (2008).
N. Potenza et al., Hybridase activity of human ribonuclease-1 revealed by a real-time fluorometric assay, Nucleic Acids Research, 18:321-7 (2006).