The 5' untranslated regions of the rat A2A adenosine receptor gene function as negative translational regulators.
The rat A2A adenosine receptor (A2A-R) gene contains two promoters, P1 and P2, which produce transcript 1 and transcript 2, respectively. These transcripts differ in the lengths of their 5' untranslated regions (5'UTR1: 514 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 present in various tissues at different levels, whereas transcript 1 is found only in the striatum. In the striatum, the level of transcript 2 is approximately 300-fold higher than that of transcript 1. The 5'UTR of both transcripts suppresses the expression of A2A-R and a firefly luciferase reporter gene at the translational level; this suppression is not observed after mutational inactivation of an "out-of-frame" upstream AUG codon. Translational suppression by the 5'UTR was also confirmed in cells using a bicistronic strategy. Collectively, these data suggest that P2 is the major promoter of the rat A2A-R gene. The 5'UTR of the rat A2A-R gene exerts an inhibitory effect on translation by an upstream open reading frame. Because the 5'UTR of the A2A-R gene possesses strong interspecies homology, translational suppression may be a general mechanism by which the expression of the A2A-R gene is regulated.
Lee
Y C
YC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Chang
C W
CW
Su
C W
CW
Lin
T N
TN
Sun
S H
SH
Lai
H L
HL
Chern
Y
Y
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation; D005796:Genes; D005910:Glioma; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D016716:PC12 Cells; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D016415:Sequence Alignment; D014162:Transfection; D014407:Tumor Cells, Cultured; D020506:Untranslated Regions
D018047:Receptors, Purinergic P1; D020506:Untranslated Regions; D008156:Luciferases