Alternative titles; symbols
HGNC Approved Gene Symbol: RNASE1
Cytogenetic location: 14q11.2 Genomic coordinates (GRCh38): 14:20,801,228-20,802,844 (from NCBI)
Pancreatic ribonuclease (EC 3.1.27.5) is one of the digestive enzymes secreted in abundance by the pancreas.
Seno et al. (1994) isolated RNASE1 from a pancreas cDNA library. The 128-amino acid mature protein contains a 28-amino acid signal peptide.
Elliott et al. (1986) mapped the mouse gene to chromosome 14 by Southern blot analysis of genomic DNA from recombinant inbred strains of mice, using a probe isolated from a pancreatic cDNA library with the rat cDNA. A polymorphic BamHI site was used to demonstrate complete concordance of the Rib-1 locus with Tcra and Np-2, encoding the alpha subunit of the T-cell receptor (see 186880) and purine nucleoside phosphorylase (164050), respectively. The assignment to mouse 14 and the close linkage to the other 2 loci was confirmed by study of one of Snell's congenic strains: the 3 loci went together. Elliott et al. (1986) predicted that the homologous human gene RIB1 is on chromosome 14.
By genomic sequence analysis, Zhang et al. (2002) mapped the RNASE1 gene to chromosome 14q11.2, where it is linked to 7 other RNase A superfamily genes. The authors noted that the entire RNase A cluster spans 368 kb.
Human pancreatic RNase is monomeric and is devoid of any biologic activity other than its RNA degrading ability. Piccoli et al. (1999) engineered the monomeric form into a dimeric protein with cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on human and mouse normal cells. The dimeric variant of human pancreatic RNase selectively sensitized cells derived from a human thyroid tumor to apoptotic death. Because of its selectivity for tumor cells, and because of its human origin, this protein was thought to represent an attractive tool for anticancer therapy.
Complete genome sequences of over 50 representative species revealed the many duplicated genes in all 3 domains of life. Zhang et al. (2002) studied the roles of gene duplication in organismal adaptation and biodiversity and the evolutionary forces behind the functional divergence of duplicated genes. They used both computational and experimental approaches in the study of RNASE1 and its duplicated gene RNASE1B in a leaf-eating colobine monkey, douc langur. They showed that RNASE1B evolved rapidly under positive selection for enhanced ribonucleolytic activity in an altered microenvironment, a response to increased demands for the enzyme for digesting bacterial RNA. At the same time, the ability to degrade double-stranded RNA, a nondigestive activity characteristic of primate RNASE1, was lost in RNASE1B, indicating functional specialization and relaxation of purifying selection. The findings demonstrated the contribution of gene duplication to organismal adaptation and showed the power of combining sequence analysis and functional assays in delineating the molecular basis of adaptive evolution.
Elliott, R. W., Samuelson, L. C., Lambert, M. S., Meisler, M. H. Assignment of pancreatic ribonuclease gene to mouse chromosome 14. Cytogenet. Cell Genet. 42: 110-112, 1986. [PubMed: 3013507] [Full Text: https://doi.org/10.1159/000132261]
Piccoli, R., Di Gaetano, S., De Lorenzo, C., Grauso, M., Monaco, C., Spalletti-Cernia, D., Laccetti, P., Cinatl, J., Matousek, J., D'Alessio, G. A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells. Proc. Nat. Acad. Sci. 96: 7768-7773, 1999. [PubMed: 10393896] [Full Text: https://doi.org/10.1073/pnas.96.14.7768]
Seno, M., Futami, J., Kosaka, M., Seno, S., Yamada, H. Nucleotide sequence encoding human pancreatic ribonuclease. Biochim. Biophys. Acta 1218: 466-468, 1994. [PubMed: 8049276] [Full Text: https://doi.org/10.1016/0167-4781(94)90208-9]
Zhang, J., Dyer, K. D., Rosenberg, H. F. RNase 8, a novel RNase A superfamily ribonuclease expressed uniquely in placenta. Nucleic Acids Res. 30: 1169-1175, 2002. [PubMed: 11861908] [Full Text: https://doi.org/10.1093/nar/30.5.1169]
Zhang, J., Zhang, Y., Rosenberg, H. F. Adaptive evolution of a duplicated pancreatic ribonuclease gene in a leaf-eating monkey. Nature Genet. 30: 416-420, 2002. [PubMed: 11925568] [Full Text: https://doi.org/10.1038/ng859]