Article abstract
Nature Structural & Molecular Biology 16, 42 - 48 (2008)
Published online: 21 December 2008 | doi:10.1038/nsmb.1535
ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8
Corina Maeder1,3, Alan K Kutach1,2,3 & Christine Guthrie1
Abstract
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.
- Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Genentech Hall, San Francisco, California 94143, USA.
- Present address: Roche Palo Alto, 3431 Hillview Ave, Palo Alto, California 94394, USA.
- These authors contributed equally to this work.
Correspondence to: Christine Guthrie1 e-mail: christineguthrie@gmail.com
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