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)

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    1 Citation (Scopus)


    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
    Issue number10
    Publication statusPublished - 29 Oct 2012

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology
    • General Agricultural and Biological Sciences
    • General


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