Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.
Synaptic plasticity is modulated by differential regulation of transcription factors such as EGR1 which binds to DNA via a zinc finger binding domain. Inactivation of EGR1 has implicated this gene as a key regulator of memory formation and learning. However, it remains puzzling how synaptic input can lead to an up-regulation of the EGR-1 protein within only a few minutes. Here, we show by immunohistochemical staining that the EGR-1 protein is localized in synapses throughout the mouse retina. We demonstrate for the first time that two variants of Egr-1 mRNA are produced in the retina by alternative polyadenylation, with the longer version having an additional 293 base pairs at the end of the 3'UTR. Remarkably, the use of the alternative polyadenylation site is controlled by light. The additional 3'UTR sequence of the longer variant displays an even higher level of phylogenetic conservation than the coding region of this highly conserved gene. Additionally, it harbours a cytoplasmic polyadenylation element which is known to respond to NMDA receptor activation. The longer version of the Egr-1 mRNA could therefore rapidly respond to excitatory stimuli such as light or glutamate release whereas the short variant, which is predominantly expressed and contains the full coding sequence, lacks the regulatory elements for cytoplasmic polyadenylation in its 3'UTR.
Simon
Perikles
P
Department of Neuroophthalmology and Pathophysiology of the Eye, Section of Neurobiology of the Eye, University of Tübingen, Germany. perikles@uni-tuebingen.de
Schott
Klaus
K
Williams
Robert W
RW
Schaeffel
Frank
F
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D017781:Genes, Immediate-Early / Q000502:physiology; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation / Q000379:methods*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors