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Journal Article

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

MPS-Authors
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Mozaffari-Jovin,  S.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Will,  C. L.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Lührmann,  R.
Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Citation

Mozaffari-Jovin, S., Wandersleben, T., Santos, K. F., Will, C. L., Lührmann, R., & Wahl, M. C. (2013). Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science, 341(6141), 80-84. doi:10.1126/science.1237515.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-18EA-4
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.