Translational regulation of GluR2 mRNAs in rat hippocampus by alternative 3' untranslated regions.
Translational regulation of GluR2 mRNAs in rat hippocampus by alternative 3' untranslated regions.
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DOI：
10.1111/j.1471-4159.2009.05992.x
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发表时间：
2009-04
影响因子：
4.7
通讯作者：
Dingledine R
中科院分区：
文献类型：
--
作者：
Irier HA;Shaw R;Lau A;Feng Y;Dingledine R
GluR2亚基决定了谷氨酸受体AMPA亚型的许多功能特性。非翻译区（UTRs）在mRNA稳定性、转运或翻译中的作用越来越被认识到。GluR2转录本的3 ‘端被交替加工形成一个短的和长的3’UTR，在哺乳动物大脑中产生两个分别为4 kb和6 kb长度的GluR2 mRNA库。然而，这些替代的3 ' utr在GluR2表达中的作用尚未报道。我们证明，在大鼠海马细胞质中，携带长3'UTR的天然GluR2 mrna大多保留在无核糖体信使核糖核蛋白（mRNP）的翻译休眠复合物中，而携带短3'UTR的GluR2转录本主要与积极翻译核糖体相关。在匹罗卡品诱导的癫痫持续状态（SE）后1天，大鼠海马中GluR2长、短转录本水平均显著降低。然而，在SE后，携带长3'UTR的GluR2 mRNA从未翻译的mRNP复合物转变为含有核糖体的复合物，这表明长3'UTR介导了GluR2 mRNA的选择性翻译抑制。在爪蟾卵母细胞中，携带替代GluR2 3'UTR的萤火虫荧光素酶报告基因的表达证实了长3'UTR足以抑制翻译。在检查的时间段内，GluR2的5 ‘或3 ’ utr的选择对卵母细胞中报告mrna的稳定性没有显著影响。总的来说，我们的研究结果表明，GluR2 mRNA的长3'UTR足以抑制翻译，并且通过长3'UTR抑制GluR2翻译的证据强烈表明，存在一种调节信号机制，以其他3'UTR不同地靶向GluR2转录本。
The GluR2 subunit determines many of the functional properties of the AMPA 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, after SE GluR2 mRNAs bearing long 3′UTRs were shifted from untranslating mRNP complexes to ribosome-containing complexes, 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.
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