Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1 Journal Article
| Authors: | Teplova, M.; Malinina, L.; Darnell, J. C.; Song, J.; Lu, M.; Abagyan, R.; Musunuru, K.; Teplov, A.; Burley, S. K.; Darnell, R. B.; Patel, D. J. |
| Article Title: | Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1 |
| Abstract: | Nova onconeural antigens are neuron-specific RNA-binding proteins implicated in paraneoplastic opsoclonus-myoclonus-ataxia (POMA) syndrome. Nova harbors three K-homology (KH) motifs implicated in alternate splicing regulation of genes involved in inhibitory synaptic transmission. We report the crystal structure of the first two KH domains (KH1/2) of Nova-1 bound to an in vitro selected RNA hairpin, containing a UCAG-UCAC high-affinity binding site. Sequence-specific intermolecular contacts in the complex involve KH1 and the second UCAC repeat, with the RNA scaffold buttressed by interactions between repeats. Whereas the canonical RNA-binding surface of KH2 in the above complex engages in protein-protein interactions in the crystalline state, the individual KH2 domain can sequence-specifically target the UCAC RNA element in solution. The observed antiparallel alignment of KH1 and KH2 domains in the crystal structure of the complex generates a scaffold that could facilitate target pre-mRNA looping on Nova binding, thereby potentially explaining Nova's functional role in splicing regulation. © 2011 Elsevier Ltd. |
| Journal Title: | Structure |
| Volume: | 19 |
| Issue: | 7 |
| ISSN: | 0969-2126 |
| Publisher: | Cell Press |
| Date Published: | 2011-07-13 |
| Start Page: | 930 |
| End Page: | 944 |
| Language: | English |
| DOI: | 10.1016/j.str.2011.05.002 |
| PROVIDER: | scopus |
| PMCID: | PMC3134789 |
| PUBMED: | 21742260 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: STRUE" - "Source: Scopus" |
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