These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Correction of disease-associated exon skipping by synthetic exon-specific activators.
    Author: Cartegni L, Krainer AR.
    Journal: Nat Struct Biol; 2003 Feb; 10(2):120-5. PubMed ID: 12524529.
    Abstract:
    Differential exon use is a hallmark of alternative splicing, a prevalent mechanism for generating protein isoform diversity. Many disease-associated mutations also affect pre-mRNA splicing, usually causing inappropriate exon skipping. SR proteins are essential splicing factors that recognize exonic splicing enhancers and drive exon inclusion. To emulate this function of SR proteins, we designed small chimeric effectors comprising a minimal synthetic RS domain covalently linked to an antisense moiety that targets an exon by Watson-Crick base pairing. Here we show that such synthetic effectors can mimic the functions of SR proteins and specifically restore wild type splicing when directed to defective BRCA1 or SMN2 pre-mRNA transcripts. This general approach can be used as a tool to investigate splicing mechanisms and modulate alternative splicing of specific genes, and as a therapeutic strategy to correct splicing defects responsible for numerous diseases.
    [Abstract] [Full Text] [Related] [New Search]