Sequences of the non-coding RNA, NTAB, are contained within the 3'-UTR of human and rat EAAT2/GLT-1 transcripts and act as transcriptional enhancers.
In the CNS, extracellular glutamate is predominantly cleared by astroglial cells through the high-affinity glutamate transporter subtype, EAAT2/GLT-1. Expression of EAAT2/GLT-1 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 glutamate-induced brain damage could be prevented by restoring glutamate homeostasis in the injured brain, spurred considerable interest in identifying the mechanisms controlling EAAT2/GLT-1 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/GLT-1 gene is strikingly similar in rat and man, little information is available on the function of the EAAT2/GLT-1 3'-UTR in the control of EAAT2/GLT-1 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/GLT-1 gene which we identified as a partial sequence of the putative non-coding RNA, Ntab. We further demonstrate that fragments of Ntab act as enhancers of EAAT2/GLT-1 transcription. Finally, we unravel that partial Ntab sequences are selectively present in the vicinity of the EAAT2/GLT-1 gene in several other mammalians, implying a conserved function of this sequence in the vertebrate CNS.
Institute of Anatomy, Medical Faculty, University of Leipzig, Germany.
Stefanie
S
Bette
Tina
T
Unger
Nicole
N
Lakowa
Maik
M
Friedrich
Jürgen
J
Engele
D020413:3' Untranslated Regions; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D001483:Base Sequence; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D020413:3' Untranslated Regions; D027342:Excitatory Amino Acid Transporter 2; D022661:RNA, Untranslated