ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8.
The spliceosome is a highly dynamic machine requiring multiple RNA-dependent ATPases of the DExD/H-box family. A fundamental unanswered question is how their activities are regulated. Brr2 function is necessary for unwinding the U4/U6 duplex, a step essential for catalytic activation of the spliceosome. Here we show that Brr2-dependent dissociation of ... U4/U6 snRNAs in vitro is activated by a fragment from the C terminus of the U5 snRNP protein Prp8. In contrast to its helicase-stimulating activity, this fragment inhibits Brr2 U4/U6-dependent ATPase activity. Notably, U4/U6 unwinding activity is not stimulated by fragments carrying alleles of prp8 that in humans confers an autosomal dominant form of retinitis pigmentosa. Because Brr2 activity must be restricted to prevent premature catalytic activation, our results have important implications for fidelity maintenance in the spliceosome.
Mesh Terms:
Adenosine Triphosphate, Carrier Proteins, Genes, Dominant, Humans, Mutation, Peptide Fragments, Protein Denaturation, RNA Helicases, RNA Splicing, RNA, Fungal, Recombinant Proteins, Retinitis Pigmentosa, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spliceosomes
Adenosine Triphosphate, Carrier Proteins, Genes, Dominant, Humans, Mutation, Peptide Fragments, Protein Denaturation, RNA Helicases, RNA Splicing, RNA, Fungal, Recombinant Proteins, Retinitis Pigmentosa, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Spliceosomes
Nat. Struct. Mol. Biol.
Date: Jan. 01, 2009
PubMed ID: 19098916
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