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
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
PubMed ID: 23704370
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