Translational regulation of GluR2 mRNAs in rat hippocampus by alternative 3' untranslated regions.

The glutamate receptor 2 (GluR2) subunit determines many of the functional properties of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate subtype of glutamate receptor. The roles of untranslated regions (UTRs) in mRNA stability, transport, or translation are increasingly recognized. The 3' end of the GluR2 transcripts are alternatively processed to form a short and long 3'UTR, giving rise to two pools of GluR2 mRNA of 4 and 6 kb in length, respectively, in the mammalian brain. However, the role of these alternative 3'UTRs in GluR2 expression has not been reported. We demonstrate that in the cytoplasm of rat hippocampus, native GluR2 mRNAs bearing the long 3'UTR are mostly retained in translationally dormant complexes of ribosome-free messenger ribonucleoprotein (mRNP), whereas GluR2 transcripts bearing the short 3'UTR are predominantly associated with actively translating ribosomes. One day after pilocarpine-induced status epilepticus (SE), the levels of both long and short GluR2 transcripts were markedly decreased in rat hippocampus. However, GluR2 mRNAs bearing the long 3'-UTRs were shifted from untranslating mRNP complexes to ribosome-containing complexes after SE, pointing to a selective translational derepression of GluR2 mRNA mediated by the long 3'UTR. In Xenopus oocytes, expression of firefly luciferase reporters bearing alternative GluR2 3'UTRs confirmed that the long 3'UTR is sufficient to suppress translation. The stability of reporter mRNAs in oocytes was not significantly influenced by alternative 5' or 3'UTRs of GluR2 over the time period examined. Overall, our findings that the long 3'UTR of GluR2 mRNA alone is sufficient to suppress translation, and the evidence for seizure-induced derepression of translation of GluR2 via the long 3'UTR strongly suggests that a regulatory signaling mechanism exists that differentially targets GluR2 transcripts with alternative 3'UTRs.