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Science. 2013 Jul 5;341(6141):80-4. doi: 10.1126/science.1237515. Epub 2013 May 23.

Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8.

Author information

1
Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

Abstract

The Ski2-like RNA helicase Brr2 is a core component of the spliceosome that must be tightly regulated to ensure correct timing of spliceosome activation. Little is known about mechanisms of regulation of Ski2-like helicases by protein cofactors. Here we show by crystal structure and biochemical analyses that the Prp8 protein, a major regulator of the spliceosome, can insert its C-terminal tail into Brr2's RNA-binding tunnel, thereby intermittently blocking Brr2's RNA-binding, adenosine triphosphatase, and U4/U6 unwinding activities. Inefficient Brr2 repression is the only recognizable phenotype associated with certain retinitis pigmentosa-linked Prp8 mutations that map to its C-terminal tail. Our data show how a Ski2-like RNA helicase can be reversibly inhibited by a protein cofactor that directly competes with RNA substrate binding.

PMID:
23704370
DOI:
10.1126/science.1237515
[Indexed for MEDLINE]
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