Aw. Li et Pr. Murphy, Expression of alternatively spliced FGF-2 antisense RNA transcripts in thecentral nervous system: regulation of FGF-2 mRNA translation, MOL C ENDOC, 162(1-2), 2000, pp. 69-78
The fibroblast growth factor-2 (FGF-2) gene is bidirectionally transcribed
to produce the FGF-2 mRNA and a 1.5 kb antisense (FGF-AS) transcript comple
mentary to the 3' unpop popd region of the FGF-2 transcript. The FGF-AS RhT
A has been postulated to play a role in the post-transcriptional regulation
of FGF-2, but this function has not been conclusively demonstrated. We cha
racterized FGF-AS cDNAs from rat brain and C6 glioma cells. and investigate
d their role in regulation of FGF-2 expression. Three FGF-AS cDNAs were iso
lated: the full-length FGF-AS mRNA and two alternative splice variants lack
ing exon 2 or exons 2 and 3 of the FGF-AS sequence. The alternatively splic
ed FGF-AS RNAs are widely expressed in the CNS, whereas liver predominantly
expressed the full-length transcript. The full-length and first splice var
iant encode 35 and 28 kDa isoforms of GFG, a MutT-related nuclear protein,
whereas the second splice variant was not pop popd. The effect of FGF-AS RN
A on FGF-2 expression was evaluated in stable C6 transfectants over-express
ing the full-length or alternatively spliced FGF-AS RNA forms. All three co
nstructs suppressed cellular FGF-7 protein (but not FGF-2 mRNA) levels, and
this effect correlated directly with the level of FGF-AS RNA. Cellular FGF
receptor content was increased and cell proliferation inhibited compared t
o wild type or. vector-transfected cells, indicating disruption of the FGF-
2 autocrine pathway by FGF-AS RNA. These findings demonstrate for the first
time that the FGF-AS RNA regulates FGF-2 expression in mammalian cells, an
d suggest that this effect is exerted predominantly at the level of transla
tion. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.