FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity
FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity
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DOI：
10.1016/s0303-7207(97)00148-2
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发表时间：
1997-10-20
影响因子：
4.1
通讯作者：
Murphy, PR
中科院分区：
文献类型：
--
作者：
Li, AW;Catherine, KTL;Murphy, PR
碱性成纤维细胞生长因子（FGF-2）基因的双向转录产生多个聚腺苷酸化正义mRNA和与FGF-2 mRNA的3 '非翻译区互补的独特的1.5kb反义转录物（FGF-AS）。大鼠FGF-AS cDNA编码一种新的35 kDa核蛋白（GFG），与抗突变NTPases的MutT家族具有同源性。针对GFG推导的氨基酸序列的抗体在成年大鼠肝细胞核中检测到强烈的免疫反应性。亚细胞分级分离和Western印迹证实了35 kDa的免疫反应性蛋白质的存在下，在细胞核部分，并在较小程度上，在大鼠肝匀浆的线粒体组分。重组GFG可抑制MutT缺陷型大肠杆菌的自发突变率。coli中进行互补测定。包含MutT结构域的53个氨基酸的框内缺失消除了该活性，证实了该区域在FGF反义基因产物中的催化功能。这些发现首次证明FGF-AS转录本编码具有MutT相关酶活性的功能性核蛋白。(C)1997 Elsevier Science爱尔兰有限公司
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. (C) 1997 Elsevier Science Ireland Ltd.