Yc. Lee et al., The 5 ' untranslated regions of the rat A(2A) adenosine receptor gene function as negative translational regulators, J NEUROCHEM, 73(5), 1999, pp. 1790-1798
The rat A(2A) adenosine receptor (A(2A)-R) gene contains two promoters, P1
and P2, which produce transcript 1 and transcript 2, respectively. These tr
anscripts differ in the lengths of their 5' untranslated regions (5'UTR1: 5
14 bp, initiated from P1; 5'UTR2: 221 bp, initiated from P2) but encode the
same protein. In the present study, we demonstrate that transcript 2 is pr
esent in various tissues at different: levels, whereas transcript 1 is foun
d only in the striatum. In the striatum, the level of transcript 2 is simil
ar to 300-fold higher than that of transcript 1. The 5'UTR of both transcri
pts suppresses the expression of A(2A)-R and a firefly luciferase reporter
gene at the translational level; this suppression is not observed after mut
ational inactivation of an "out-of-frame" upstream AUG codon. Translational
suppression by the 5'UTR was also confirmed in cells using a bicistronic s
trategy. Collectively, these data suggest that P2 is the major promoter of
the rat A(2A)-R gene. The 5'UTR of the rat A(2A)-R gene exerts an inhibitor
y effect on translation by an upstream open reading frame. Because the 5'UT
R of the A(2A)-R gene possesses strong interspecies homology, translational
suppression may be a general mechanism by which the expression of the A(2A
)-R gene is regulated.