Sad1 counteracts Brr2-mediated dissociation of U4/U6.U5 in tri-snRNP homeostasis.


The yeast Sad1 protein was previously identified in a screen for factors involved in the assembly of the U4/U6 di-snRNP particle. Sad1 is required for pre-mRNA splicing both in vivo and in vitro, and its human orthologue has been shown to associate with U4/U6.U5 tri-snRNP. We show here that Sad1 plays a role in maintaining a functional form of the tri-snRNP by promoting the association of U5 snRNP with U4/U6 di-snRNP. In the absence of Sad1, the U4/U6.U5 tri-snRNP dissociates into U5 and U4/U6 upon ATP hydrolysis and cannot bind to the spliceosome. The separated U4/U6 and U5 can reassociate upon incubation more favorably in the absence of ATP and in the presence of Sad1. Brr2 is responsible for mediating ATP-dependent dissociation of the tri-snRNP. Our results demonstrate a role of Sad1 in maintaining the integrity of the tri-snRNP by counteracting Brr2-mediated dissociation of tri-snRNP and provide insights into homeostasis of the tri-snRNP.

DOI: 10.1128/MCB.00837-13
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@article{Huang2014Sad1CB, title={Sad1 counteracts Brr2-mediated dissociation of U4/U6.U5 in tri-snRNP homeostasis.}, author={Yu-hsin Huang and Che-Sheng Chung and D Kao and T L Kao and Soo-Chen Cheng}, journal={Molecular and cellular biology}, year={2014}, volume={34 2}, pages={210-20} }