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Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly

Abstract

Recent studies indicate that splicing of pre-messenger RNA and export of mRNA are normally coupled in vivo1,2,3,4,5,6. During splicing, the conserved mRNA export factor Aly is recruited to the spliced mRNA–protein complex (mRNP), which targets the mRNA for export. At present, it is not known how Aly is recruited to the spliced mRNP. Here we show that the conserved DEAD-box helicase UAP56, which functions during spliceosome assembly7,8,9,10, interacts directly and highly specifically with Aly. Moreover, UAP56 is present together with Aly in the spliced mRNP. Significantly, excess UAP56 is a potent dominant negative inhibitor of mRNA export. Excess UAP56 also inhibits the recruitment of Aly to the spliced mRNP. Furthermore, a mutation in Aly that blocks its interaction with UAP56 prevents recruitment of Aly to the spliced mRNP. These data suggest that the splicing factor UAP56 functions in coupling the splicing and export machineries by recruiting Aly to the spliced mRNP.

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Figure 1: The mRNA export factor Aly interacts with the splicing factor UAP56.
Figure 2: UAP56 is present in the spliced mRNP.
Figure 3: Excess UAP56 inhibits mRNA export.
Figure 4: UAP56 recruits Aly to the spliced mRNP.
Figure 5: The UAP56–Aly interaction is required for Aly recruitment to the spliced mRNP.

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Acknowledgements

We are grateful to M. Green for the UAP56 and His-BEF cDNAs and UAP56 antibody, to R. Grosschedl for the GST–Aly clone, to D. Moazed for the GST–Sir2 clone, and to A. Nunez-Roldan for the Aly antibody. We are indebted to D. Dorman, B. Lee and S. Lee for discussion and comments on the manuscript. We thank B. Lee for providing the GST–Aly ΔRGG protein. J.R. is a Marie Curie Fellow. M.M. was supported by a grant from the Danish National Research Foundation.

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Correspondence to Robin Reed.

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Luo, MJ., Zhou, Z., Magni, K. et al. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature 413, 644–647 (2001). https://doi.org/10.1038/35098106

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