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A Ran-independent pathway for export of spliced mRNA

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Abstract

All major nuclear export pathways so far examined follow a general paradigm1,2,3. Specifically, a complex is formed in the nucleus, containing the export cargo, a member of the importin-β family of transporters and RanGTP. This complex is translocated across the nuclear pore to the cytoplasm, where hydrolysis of the GTP on Ran is stimulated by the GTPase-activating protein RanGAP4,5. The activity of RanGAP is increased by RanBP1, which also promotes disassembly of RanGTP–cargo–transporter complexes6,7. Here we investigate the role of RanGTP in the export of mRNAs generated by splicing. We show that nuclear injection of a Ran mutant (RanT24N)8 or the normally cytoplasmic RanGAP potently inhibits the export of both tRNA and U1 snRNA9, but not of spliced mRNAs. Moreover, nuclear injection of RanGAP together with RanBP1 blocks tRNA export but does not affect mRNA export. These and other data indicate that export of spliced mRNA is the first major cellular transport pathway that is independent of the export co-factor Ran.

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Figure 1: Export of tRNA and U1 snRNA, but not spliced mRNA, is blocked by nuclear injection of RanGAP.
Figure 2: Kinetics of export of tRNA, U1 snRNA and spliced mRNA after nuclear injection of Ran mutants.
Figure 3: Export of spliced mRNA is not affected by the combination of RanGAP and RanBP1.
Figure 4: Ran is not detected in purified spliceosomes or the spliced mRNP.

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Acknowledgements

We thank E. Hurt, H. Grosshans, K. Magni and R. Das for useful discussions and critical comments on the manuscript. We thank E. Hurt, I. Mattaj, D. Görlich, and Y. Yoneda for reagents. This work was supported by an NIH grant to R.R.

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  1. K. Nicole Clouse and Ming-juan Luo: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, 02115, Massachusetts, USA

    K. Nicole Clouse, Ming-juan Luo, Zhaolan Zhou & Robin Reed

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  1. K. Nicole Clouse
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  2. Ming-juan Luo
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  3. Zhaolan Zhou
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  4. Robin Reed
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Correspondence to Robin Reed.

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Clouse, K., Luo, Mj., Zhou, Z. et al. A Ran-independent pathway for export of spliced mRNA. Nat Cell Biol 3, 97–99 (2001). https://doi.org/10.1038/35050625

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