Identification of peptide inhibitors of pre-mRNA splicing derived from the essential interaction domains of CDC5L and PLRG1

Paul Ajuh, Angus I. Lamond

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    CDC5L and PLRG1 are both spliceosomal proteins that are highly conserved across species. They have both been shown to be part of sub- spliceosomal protein complexes that are essential for pre-mRNA splicing in yeast and humans. CDC5L and PLRG1 interact directly in vitro. This interaction is mediated by WD40 regions in PLRG1 and the C-terminal domain of CDC5L. In order to determine whether this interaction is important for the splicing mechanism, we have designed peptides corresponding to highly conserved sequences in the interaction domains of both proteins. These peptides were used in in vitro splicing experiments as competitors to the cognate sequences in the endogenous proteins. Certain peptides derived from the binding domains of both proteins were found to inhibit in vitro splicing. This splicing inhibition could be prevented by preincubating the peptides with the corresponding partner protein that had been expressed in Escherichia coli. The results from this study indicate that the interaction between CDC5L and PLRG1 is essential for pre-mRNA splicing and further demonstrate that small peptides can be used as effective splicing inhibitors.
    Original languageEnglish
    Pages (from-to)6104-6116
    Number of pages13
    JournalNucleic Acids Research
    Volume31
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 2003

    Keywords

    • Amino Acid Sequence
    • Binding Sites
    • Cell Cycle Proteins
    • Cell Extracts
    • Cell Nucleus
    • Conserved Sequence
    • HeLa Cells
    • Humans
    • Intracellular Signaling Peptides and Proteins
    • Molecular Sequence Data
    • Nuclear Proteins
    • Peptide Fragments
    • Protein Binding
    • Protein Structure, Tertiary
    • RNA Precursors
    • RNA Splicing
    • Sequence Alignment
    • Spliceosomes
    • Substrate Specificity

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