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

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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Binding, Competitive, Carrier Proteins, Humans, Molecular Sequence Data, Mutation, Protein Structure, Tertiary, RNA, RNA Helicases, RNA-Binding Proteins, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Ribonucleoproteins, Small Nuclear, Saccharomyces cerevisiae Proteins, Spliceosomes, Substrate Specificity
Science
Date: Jul. 05, 2013
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