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Gene Section
Mini Review
RNASET2 (ribonuclease T2)
Francesco Acquati, Paola Campomenosi
Dipartimento di Biotecnologie e Scienze Molecolari, Universita degli Studi dell'Insubria, I-21100 Varese,
Italy
Published in Atlas Database: February 2007
Online updated version: http://AtlasGeneticsOncology.org/Genes/RNASET2ID518ch6q27.html
DOI: 10.4267/2042/38446
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology
kb of genomic DNA. The translation initiation codon is
located to exon 1 and the stop codon to exon 9. Exons
III and VI encode the two CAS motifs (Catalytic
Active Sites) responsible for the ribonuclease activity
of the RNASET2 protein.
Identity
Hugo: RNASET2
Other
names:
RNASE6PL;
RP11-514O12.3;
bA514O12.3
Location: 6q27
Local order: Telomeric to RPS6KA2, centromeric to
FGFR1OP.
Note: This gene is the first human member of the
Rh/T2/S-glycoprotein
family
of
extracellular
ribonucleases. It is a putative class II tumor suppressor
gene potentially involved in the pathogenesis of several
solid and haematologic human neoplasias such as
ovarian cancer, melanoma and non-Hodgkin
lymphoma.
Transcription
The RNASET2 gene is transcribed in the telomere-tocentromere orientation to produce an ubiquitously
expressed mRNA approximately 1,4 kb in length. EST
clones representing splice variants of the same gene
have been described.
Pseudogene
A processed pseudogene showing 85% identity with
RNASET2 mRNA maps to chromosome 7p11.2. The
expression pattern of this pseudogene is not known.
DNA/RNA
Description
This gene is split in 9 exons spanning approximatly 27
I-IX: RNASET2 exons.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3)
219
RNASET2 (ribonuclease T2)
Acquati F, Campomenosi P
tumorigenicity and metastasis when overexpressed in
the same ovarian cancer cell lines. Such results have
been recently confirmed in a human melanoma cell
line.
Protein
Description
The full-length RNASET2 protein contains 256
aminoacids and displays an apparent MW of 36 kDa in
its secreted form. Two 31 and 27 kDa C-terminal
proteolytic products have also been observed
intracellularly in several human cancer cell lines and
localize to the lysosome.
Homology
The primary sequenze of RNASET2 shows strong
homology to the Rh/T2/S family of secreted
ribonucleases.
Mutations
Expression
Expression of the RNASET2 protein has been detected
in several human ovarian cancer cell lines and in some
melanoma, prostate, pancreatic and breast carcinoma
cell lines.
Germinal
A common exon-9 missense C708T germline mutation
has been described but no evidence for an association
of this allele with human cancer was found.
Localisation
Somatic
The RNASET2 protein can be detected either
intracellularly within lysosomes and secretory pathway,
or extracellularly in a secreted form (in cell culture
supernatants).
A few common polymorphisms in exons 1, 8 and 9
have been described.
Implicated in
Function
Human ovarian carcinoma
Biochemical function: RNASET2 is an acid
ribonuclease with optimal activity at pH 5 and
preferential cleavage of poly-A and poly-U homopolyribonucleotides.
Biological function: RNASET2 behaves as a class II
tumor suppressor gene for ovarian cancer, since
experimental overexpression of this gene in human
ovarian cancer cell lines is associated with a significant
decrease of their tumorigenic and metastasizing
potential in vivo. Strikingly, the ribonuclease catalytic
activity is apparently dispensable for RNASET2 to play
such antioncogenic role. Indeed, a double CAS mutant
cDNA construct encoding an almost inactive
RNASET2 protein is still able to suppress
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3)
Disease
Loss of expression of RNASET2 occurs in a significant
fraction of human ovarian cancer cell lines and primary
ovarian tumours. When overexpressed by gene transfer
experiments in human ovarian cancer cell lines
displaying a low level of endogenous mRNA,
RNASET2 strongly suppresses the tumorigenic and
metastatic potential of these cell lines in vivo.
Cytogenetics
The RNASET2 genes maps in a genomic region (6q27)
which is frequently deleted or otherwise rearranged in a
wide range of human neoplasias, including ovarian
cancer.
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RNASET2 (ribonuclease T2)
Acquati F, Campomenosi P
References
localization of the human homolog of the R2/Th/Stylar
ribonuclease gene family. Methods Mol Biol 2001;160:87-101.
Trubia M, Sessa L, Taramelli R. Mammalian Rh/T2/Sglycoprotein ribonuclease family genes: cloning of a human
member located in a region of chromosome 6 (6q27) frequently
deleted in human malignancies. Genomics 1997;42:342-344.
Acquati F, Possati L, Ferrante L, Campomenosi P, Talevi S,
Bardelli S, Margiotta C, Russo A, Bortoletto E, Rocchetti R,
Calza R, Cinquetti R, Monti L, Salis S, Barbanti-Brodano G,
Taramelli R. Tumor and metastasis suppression by the human
RNASET2 gene. Int J Oncol 2005;26:1159-1168.
Acquati F, Morelli C, Cinquetti R, Bianchi MG, Porrini D,
Varesco L, Gismondi V, Rocchetti R, Talevi S, Possati L,
Magnanini C, Tibiletti MG, Bernasconi B, Daidone MG,
Shridhar V, Smith DI, Negrini M, Barbanti-Brodano G,
Taramelli R. Cloning and characterization of a senescence
inducing and class II tumor suppressor gene in ovarian
carcinoma at chromosome region 6q27. Oncogene
2001;20:980-988.
Campomenosi P, Salis S, Lindqvist C, Mariani D, Nordström T,
Acquati F, Taramelli R. Characterization of RNASET2, the first
human member of the Rh/T2/S family of glycoproteins. Arch
Biochem Biophys 2006;449:17-26.
This article should be referenced as such:
Acquati F, Campomenosi P. RNASET2 (ribonuclease T2).
Atlas Genet Cytogenet Oncol Haematol.2007;11(3):219-221.
Acquati F, Nucci C, Bianchi MG, Gorletta T, Taramelli R.
Molecular cloning, tissue distribution, and chromosomal
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3)
221