Authors: Stefanie Bette Tina Unger Nicole Lakowa Maik Friedrich Jürgen Engele
Publish Date: 2010/11/26
Volume: 31, Issue: 3, Pages: 393-399
Abstract
In the CNS extracellular glutamate is predominantly cleared by astroglial cells through the highaffinity glutamate transporter subtype EAAT2/GLT1 Expression of EAAT2/GLT1 is perturbed in various acute and chronic brain diseases eventually allowing for the onset of neurotoxic extracellular glutamate concentrations and subsequent excitotoxic neuronal cell death The idea that glutamateinduced brain damage could be prevented by restoring glutamate homeostasis in the injured brain spurred considerable interest in identifying the mechanisms controlling EAAT2/GLT1 expression Since to date most of this study was done with rat astrocytes an emerging issue is to whether these findings would also apply to humans While so far it is known that the promoter region of the EAAT2/GLT1 gene is strikingly similar in rat and man little information is available on the function of the EAAT2/GLT1 3′UTR in the control of EAAT2/GLT1 expression in general as well as across both species We now report on the presence of a homologous sequence within the 3′UTR of the human and rat EAAT2/GLT1 gene which we identified as a partial sequence of the putative noncoding RNA Ntab We further demonstrate that fragments of Ntab act as enhancers of EAAT2/GLT1 transcription Finally we unravel that partial Ntab sequences are selectively present in the vicinity of the EAAT2/GLT1 gene in several other mammalians implying a conserved function of this sequence in the vertebrate CNS
Keywords: