FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity

Audrey W. Li; Catherine K.L. Too; Rai Knee; Michael Wilkinson; Paul R. Murphy

doi:10.1016/S0303-7207(97)00148-2

FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity

Audrey W. Li, Catherine K.L. Too, Rai Knee, Michael Wilkinson, Paul R. Murphy

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28 Citas (Scopus)

Resumen

Bidirectional transcription of the basic fibroblast growth factor (FGF-2) gene gives rise to multiple polyadenylated sense mRNAs and a unique 1.5 kb antisense transcript (FGF-AS) which is complementary to the 3'-untranslated region of the FGF-2. mRNA. The rat FGF-AS cDNA encodes a novel 35 kDa nuclear protein (GFG) with homology to the MutT family of antimutator NTPases. Antibodies against the deduced amino acid sequence of GFG detected intense immunoreactivity in the nuclei of adult rat hepatocytes. Subcellular fractionation and Western blotting confirmed the presence of a 35 kDa immunoreactive protein in the nuclear fraction and, to a lesser extent, in the mitochondrial fractions of rat liver homogenates. Recombinant GFG suppressed the spontaneous mutation rate of MutT-deficient E. coli in a complementation assay. In-frame deletion of the 53 amino acids encompassing the MutT domain eliminated this activity, confirming the catalytic function of this region in the FGF antisense gene product. These findings demonstrate for the first time that the FGF-AS transcript encodes a functional nuclear protein with MutT-related enzymatic activity.

Idioma original	English
Páginas (desde-hasta)	177-182
Número de páginas	6
Publicación	Molecular and Cellular Endocrinology
Volumen	133
N.º	2
DOI	https://doi.org/10.1016/S0303-7207(97)00148-2
Estado	Published - oct. 20 1997
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
We are very grateful to Dr Maurice Bessman for the TX48 MutT+ and SB MutT− E. coli strains and for helpful suggestions. We acknowledge Diane Wilkinson for her expert technical assistance. This work was supported by grants from the Medical Research Council of Canada (to M.W. and P.R.M), the Cancer Research Society (to P.R.M. and C.K.L.T.) and the Atlee Endowment (to P.R.M.)

ASJC Scopus Subject Areas

Biochemistry
Molecular Biology
Endocrinology

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abstract = "Bidirectional transcription of the basic fibroblast growth factor (FGF-2) gene gives rise to multiple polyadenylated sense mRNAs and a unique 1.5 kb antisense transcript (FGF-AS) which is complementary to the 3'-untranslated region of the FGF-2. mRNA. The rat FGF-AS cDNA encodes a novel 35 kDa nuclear protein (GFG) with homology to the MutT family of antimutator NTPases. Antibodies against the deduced amino acid sequence of GFG detected intense immunoreactivity in the nuclei of adult rat hepatocytes. Subcellular fractionation and Western blotting confirmed the presence of a 35 kDa immunoreactive protein in the nuclear fraction and, to a lesser extent, in the mitochondrial fractions of rat liver homogenates. Recombinant GFG suppressed the spontaneous mutation rate of MutT-deficient E. coli in a complementation assay. In-frame deletion of the 53 amino acids encompassing the MutT domain eliminated this activity, confirming the catalytic function of this region in the FGF antisense gene product. These findings demonstrate for the first time that the FGF-AS transcript encodes a functional nuclear protein with MutT-related enzymatic activity.",

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AU - Murphy, Paul R.

N1 - Funding Information: We are very grateful to Dr Maurice Bessman for the TX48 MutT+ and SB MutT− E. coli strains and for helpful suggestions. We acknowledge Diane Wilkinson for her expert technical assistance. This work was supported by grants from the Medical Research Council of Canada (to M.W. and P.R.M), the Cancer Research Society (to P.R.M. and C.K.L.T.) and the Atlee Endowment (to P.R.M.)

PY - 1997/10/20

Y1 - 1997/10/20

N2 - Bidirectional transcription of the basic fibroblast growth factor (FGF-2) gene gives rise to multiple polyadenylated sense mRNAs and a unique 1.5 kb antisense transcript (FGF-AS) which is complementary to the 3'-untranslated region of the FGF-2. mRNA. The rat FGF-AS cDNA encodes a novel 35 kDa nuclear protein (GFG) with homology to the MutT family of antimutator NTPases. Antibodies against the deduced amino acid sequence of GFG detected intense immunoreactivity in the nuclei of adult rat hepatocytes. Subcellular fractionation and Western blotting confirmed the presence of a 35 kDa immunoreactive protein in the nuclear fraction and, to a lesser extent, in the mitochondrial fractions of rat liver homogenates. Recombinant GFG suppressed the spontaneous mutation rate of MutT-deficient E. coli in a complementation assay. In-frame deletion of the 53 amino acids encompassing the MutT domain eliminated this activity, confirming the catalytic function of this region in the FGF antisense gene product. These findings demonstrate for the first time that the FGF-AS transcript encodes a functional nuclear protein with MutT-related enzymatic activity.

AB - Bidirectional transcription of the basic fibroblast growth factor (FGF-2) gene gives rise to multiple polyadenylated sense mRNAs and a unique 1.5 kb antisense transcript (FGF-AS) which is complementary to the 3'-untranslated region of the FGF-2. mRNA. The rat FGF-AS cDNA encodes a novel 35 kDa nuclear protein (GFG) with homology to the MutT family of antimutator NTPases. Antibodies against the deduced amino acid sequence of GFG detected intense immunoreactivity in the nuclei of adult rat hepatocytes. Subcellular fractionation and Western blotting confirmed the presence of a 35 kDa immunoreactive protein in the nuclear fraction and, to a lesser extent, in the mitochondrial fractions of rat liver homogenates. Recombinant GFG suppressed the spontaneous mutation rate of MutT-deficient E. coli in a complementation assay. In-frame deletion of the 53 amino acids encompassing the MutT domain eliminated this activity, confirming the catalytic function of this region in the FGF antisense gene product. These findings demonstrate for the first time that the FGF-AS transcript encodes a functional nuclear protein with MutT-related enzymatic activity.

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FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity

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ASJC Scopus Subject Areas

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