| First Author | Dredge BK | Year | 2005 |
| Journal | EMBO J | Volume | 24 |
| Issue | 8 | Pages | 1608-20 |
| PubMed ID | 15933722 | Mgi Jnum | J:98264 |
| Mgi Id | MGI:3577726 | Doi | 10.1038/sj.emboj.7600630 |
| Citation | Dredge BK, et al. (2005) Nova autoregulation reveals dual functions in neuronal splicing. EMBO J 24(8):1608-20 |
| abstractText | The Nova family of neuron-specific RNA-binding proteins were originally identified as targets in an autoimmune neurologic disease characterized by failure of motor inhibition. Nova-1 regulates alternative splicing of pre-mRNAs encoding the inhibitory neurotransmitter receptor subunits GABA(A)Rgamma2 and GlyRalpha2 by directly binding intronic elements, resulting in enhancement of exon inclusion. Here we identify exon E4 in the Nova-1 pre-mRNA itself, encoding a phosphorylated protein domain, as an additional target of Nova-dependent splicing regulation in the mouse spinal cord. Nova binding to E4 is necessary and sufficient for Nova-dependent exon exclusion. E4 harbors five repeats of the known Nova-binding tetranucleotide YCAY and mutation of these elements destroys Nova-dependent regulation. Furthermore, swapping of the sites from Nova-1 and GABA(A)Rgamma2 indicates that the ability of Nova to enhance or repress alternative exon inclusion is dependent on the position of the Nova-binding element within the pre-mRNA. These studies demonstrate that in addition to its previously described role as a splicing activator, Nova autoregulates its own expression by acting as a splicing repressor. |
