Inhibition of Pre-mRNA Splicing by a Synthetic Blom7α-Interacting Small RNA

Marlies Löscher, Markus Schosserer, Eric Dausse, Kiseok Lee, Paul M. Ajuh, Regina Grillari-Voglauer, Angus I. Lamond, Jean Jacques Toulmé, Johannes Grillari (Lead / Corresponding author)

Research output: Contribution to journalArticle

Abstract

Originally the novel protein Blom7α was identified as novel pre-mRNA splicing factor that interacts with SNEVPrp19/Pso4, an essential protein involved in extension of human endothelial cell life span, DNA damage repair, the ubiquitin-proteasome system, and pre-mRNA splicing. Blom7α belongs to the heteronuclear ribonucleoprotein K homology (KH) protein family, displaying 2 KH domains, a well conserved and widespread RNA-binding motif. In order to identify specific sequence binding motifs, we here used Systematic Evolution of Ligands by Exponential Enrichment (SELEX) with a synthetic RNA library. Besides sequence motifs like (U/A)1-4 C2-6 (U/A)1-5, we identified an AC-rich RNA-aptamer that we termed AK48 (Aptamer KH-binding 48), binding to Blom7α with high affinity. Addition of AK48 to pre-mRNA splicing reactions in vitro inhibited the formation of mature spliced mRNA and led to a slight accumulation of the H complex of the spliceosome. These results suggest that the RNA binding activity of Blom7α might be required for pre-mRNA splicing catalysis. The inhibition of in-vitro splicing by the small RNA AK48 indicates the potential use of small RNA molecules in targeting the spliceosome complex as a novel target for drug development.

Original languageEnglish
Article numbere47497
Number of pages9
JournalPLoS ONE
Volume7
Issue number10
DOIs
Publication statusPublished - 29 Oct 2012

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    Löscher, M., Schosserer, M., Dausse, E., Lee, K., Ajuh, P. M., Grillari-Voglauer, R., Lamond, A. I., Toulmé, J. J., & Grillari, J. (2012). Inhibition of Pre-mRNA Splicing by a Synthetic Blom7α-Interacting Small RNA. PLoS ONE, 7(10), [e47497]. https://doi.org/10.1371/journal.pone.0047497