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Proc Natl Acad Sci U S A
1997 May 13;9410:4943-7. doi: 10.1073/pnas.94.10.4943.
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Characterization and tissue-specific expression of the rat basic fibroblast growth factor antisense mRNA and protein.
Knee R, Li AW, Murphy PR.
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An RNA transcribed from the antisense strand of the FGF-2 gene has been implicated in the regulation of FGF-2 mRNA stability in amphibian oocytes. We have now cloned and characterized a novel 1. 1-kb mRNA (fgf-as) from neonatal rat liver. In non-central nervous system (CNS) tissues the fgf-as RNA is abundantly expressed in a developmentally regulated manner. The FGF-AS cDNA contains a consensus polyadenylylation signal and a long open reading frame (ORF) whose deduced amino acid sequence predicts a 35-kDa protein with homology to the MutT family of nucleotide hydrolases. Western blot analysis with antibodies against the deduced peptide sequence demonstrates that the FGF-AS protein is expressed in a broad range of non-CNS tissue in the postnatal period. In the developing brain, the abundance of sense and antisense transcripts are inversely related, suggesting a role for the antisense RNA in posttranscriptional regulation of FGF-2 expression in this tissue. The FGF-AS is complementary to two widely separated regions in the long 3' untranslated region of the FGF-2 mRNA, in the vicinity of the proximal and distal polyadenylylation sites. These findings demonstrate that the FGF-2 and fgf-as RNAs are coordinately transcribed on a tissue-specific and developmentally regulated basis and suggest that interaction of the sense and antisense RNAs may result in posttranscriptional regulation of FGF-2 in some tissues.
Figure 5
(Upper) Alignment of the deduced amino acid sequence of rat and Xenopus FGF-2 antisense cDNA clones. Double and single dots represent amino acid identity and similarity, respectively. Percentages of identity and similarity between rat and Xenopus antisense amino acid sequences are 69% and 89%, respectively. The location of a putative transmembrane domain (amino acids 89–107) is indicated by a heavy overline. The conserved MutT domain is shaded. (Lower) Comparison of the MutT domain and flanking sequence of the FGF-AS protein with those of other members of the MutT/Nudix family of proteins. In the consensus sequence (top line) U represents a bulky aliphatic amino acid (I, L, or V) and x may be any amino acid. Bold letters indicate identities with the rat FGF-AS protein sequence. The indicated sequences are P13420P13420 (Xenopus FGF-AS); U30313U30313 (human Ap4Aase); D49977D49977 and P36639P36639 (rat and human 8-oxo-dGTPase); Q01976Q01976 (yeast YSA1); and P08377P08377 (Escherichia coli MutT).
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