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The Journal of Neuroscience, April 7, 2004, 24(14):3489-3499; doi:10.1523/JNEUROSCI.4127-03.2004

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Cellular/Molecular
Inhibition of Glutamate Receptor 2 Translation by a Polymorphic Repeat Sequence in the 5'-Untranslated Leaders

Scott J. Myers, Yunfei Huang, Thomas Genetta, and Raymond Dingledine

Department of Pharmacology, Emory University, Atlanta, Georgia 30322

Previous studies have identified multiple transcription initiation sites for the glutamate receptor 2 (GluR2) gene, resulting in a heterogeneous population of GluR2 transcripts in vivo that differ in the length of their 5'-untranslated leaders (5'-UTR). We designed a series of monocistronic and dicistronic GluR2 cDNA constructs that model the natural in vivo transcripts and investigated their translation efficiencies in rabbit reticulocyte lysates, Xenopus oocytes, and primary cultured neurons. Transcripts containing long 5' leaders (429 and 481 bases) were translated poorly compared with those with shorter leaders (341 or fewer bases). None of the five initiation codons in the 5'-UTR or the leader length per se were responsible for translation regulation. Rather, control of translation was mediated by a sequence containing a 34–42 nucleotide imperfect GU repeat predicted to form secondary structure in vivo. This translation suppression domain is included in some but not all rat and human GluR2 transcripts in vivo, depending on the site of transcription initiation. Rat cortex GluR2 transcripts that lack the translation suppression sequence were preferentially associated with polyribosomes. Furthermore, the GU-repeat cluster was found to be polymorphic in humans, raising the possibility that expansion or contraction of the GU-repeat cluster in certain populations might modify the level of GluR2 protein expression in neurons.

Key words: GluR2; translation; polymorphism; hippocampus; GU repeat; human; AMPA receptor; untranslated; stem-loop; Gria2


Received Sep 7, 2003; revised January 22, 2004; accepted February 23, 2004.




This article has been cited by other articles:


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H. A. Irier, Y. Quan, J. Yoo, and R. Dingledine
Control of Glutamate Receptor 2 (GluR2) Translational Initiation by Its Alternative 3' Untranslated Regions
Mol. Pharmacol., December 1, 2009; 76(6): 1145 - 1149.
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L. Ma, L. Song, G. E. Radoi, and N. L. Harrison
Transcriptional Regulation of the Mouse Gene Encoding the {alpha}-4 Subunit of the GABAA Receptor
J. Biol. Chem., September 24, 2004; 279(39): 40451 - 40461.
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