DMCA
Exon silencing by UAGG motifs in response to neuronal excitation (2007)
| Venue: | PLoS Biol |
| Citations: | 12 - 1 self |
BibTeX
@ARTICLE{An07exonsilencing,
author = {Ping An and Paula J. Grabowski},
title = {Exon silencing by UAGG motifs in response to neuronal excitation},
journal = {PLoS Biol},
year = {2007},
pages = {36}
}
Share
 |
 |
 |
 |
||
OpenURL
Abstract
Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse. The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell excitation, but the molecular nature of this splicing responsiveness is not yet understood. Here we investigate the molecular basis for the induced changes in splicing of the CI cassette exon in primary rat cortical cultures in response to KCl-induced depolarization using an expression assay with a tight neuron-specific readout. In this system, exon silencing in response to neuronal excitation was mediated by multiple UAGG-type silencing motifs, and transfer of the motifs to a constitutive exon conferred a similar responsiveness by gain of function. Biochemical analysis of protein binding to UAGG motifs in extracts prepared from treated and mock-treated cortical cultures showed an increase in nuclear hnRNP A1-RNA binding activity in parallel with excitation. Evidence for the role of the NMDA receptor and calcium signaling in the induced splicing response was shown by the use of specific antagonists, as well as cell-permeable inhibitors of signaling pathways. Finally, a wider role for exon-skipping responsiveness is shown to involve additional exons with UAGGrelated silencing motifs, and transcripts involved in synaptic functions. These results suggest that, at the posttranscriptional level, excitable exons such as the CI cassette may be involved in strategies by which neurons mount adaptive responses to hyperstimulation. Citation: An P, Grabowski PJ (2007) Exon silencing by UAGG motifs in response to neuronal excitation. PLoS Biol 5(2): e36. doi:10.1371/journal.pbio.0050036
Keyphrases
neuronal excitation uagg motif exon silencing ci cassette molecular nature adaptive response wider role synaptic function constitutive exon exon-skipping responsiveness tight neuron-specific readout expression assay posttranscriptional level nmda r1 receptor calcium signaling primary rat cortical culture functional diversity nuclear hnrnp a1-rna binding activity specific antagonist biochemical analysis kcl-induced depolarization nmda receptor multiple uagg-type silencing motif induced splicing response similar responsiveness cell-permeable inhibitor plo biol mock-treated cortical culture molecular basis excitable exon induced change grabowski pj ci cassette exon additional exon
