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Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p

Abstract

The yeast nuclear protein Yra1p is an essential export factor for mRNA. Yra1p interacts directly with the mRNA transport factor Mex67p/Mtr2p, which is associated with the nuclear pore1,2. Here, we report a genetic interaction between YRA1 and SUB2, the gene for a DEAD box helicase involved in splicing3,4,5. Mutation of SUB2 as well as its overexpression leads to a defect in mRNA export. Moreover, Yra1p and Sub2p bind directly to each other both in vivo and in vitro. Significantly, Sub2p and Mex67p/Mtr2p bind to the same domains of Yra1p, and the proteins compete for binding to Yra1p. Together, these data indicate that the spliceosomal component Sub2p is also important in mRNA export and may function to recruit Yra1p to the mRNA. Sub2p may then be displaced from Yra1p by the binding of Mex67p/Mtr2p, which participates in the export of mRNA through the nuclear pores.

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Figure 1: YRA1 interacts genetically with MEX67 and SUB2.
Figure 2: Sub2p is involved in nuclear mRNA export.
Figure 3: Sub2p is involved in nuclear mRNA export of both intron-containing and intron-lacking mRNAs.
Figure 4: Yra1p interacts with Sub2p in vivo and in vitro.
Figure 5: Mex67p/Mtr2p competes with Sub2p for binding to Yra1p.

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References

  1. Segref, A. et al. Mex67p which is an essential factor for nuclear mRNA export binds to both poly(A)+ RNA and nuclear pores. EMBO J. 16, 3256–3271 (1997).

    Article  CAS  Google Scholar 

  2. Sträßer, K. & Hurt, E. C. Yra1p, a conserved nuclear RNA binding protein, interacts directly with Mex67p and is required for mRNA export. EMBO J. 19, 410–420 (2000).

    Article  Google Scholar 

  3. Libri, D., Graziani, N., Saguez, C. & Boulay, J. Multiple roles for the yeast SUB2/yUAP56 gene in splicing. Genes Dev. 15, 36–41 (2001).

    Article  CAS  Google Scholar 

  4. Zhang, M. & Green, M. R. Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. Genes Dev. 15, 30–35 (2001).

    Article  Google Scholar 

  5. Kistler, A. L. & Guthrie, C. Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for Sub2, an essential spliceosomal ATPase. Genes Dev. 15, 42–49 (2001).

    Article  CAS  Google Scholar 

  6. Portman, D. S., O'Connor, J. P. & Dreyfuss, G. Yra1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity. RNA 3, 527–537 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Hurt, E. et al. Mex67p mediates the nuclear export of a variety of pol II transcripts. J. Biol. Chem. 275, 8361–8368 (2000).

    Article  CAS  Google Scholar 

  8. Jensen, T. H., Patricio, K., McCarthy, T. & Rosbash, M. A block to mRNA nuclear export in S. cerevisiae leads to hyperadenylation of transcripts that accumulate at the site of transcription. Mol. Cell 7, 887–898 (2001).

    Article  CAS  Google Scholar 

  9. Bousquet-Antonelli, C., Presutti, C. & Tollervey, D. Identification of a regulated pathway for nuclear pre-mRNA turnover. Cell 102, 765–775 (2000).

    Article  CAS  Google Scholar 

  10. Stutz, F. et al. REF, an evolutionarily conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. RNA 6, 638–650 (2000).

    Article  CAS  Google Scholar 

  11. Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437–440 (1999).

    Article  CAS  Google Scholar 

  12. Zhou, Z. L. et al. The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans. Nature 407, 401–405 (2000).

    Article  ADS  CAS  Google Scholar 

  13. Huang, Y. & Steitz, J. A. Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol. Cell 7, 899–905 (2001).

    Article  CAS  Google Scholar 

  14. Bruhn, L., Munnerlyn, A. & Grosschedl, R. ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRα enhancer function. Genes Dev. 11, 640–653 (1997).

    Article  CAS  Google Scholar 

  15. Virbasius, C. M., Wagner, S. & Green, M. R. A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins. Mol. Cell 4, 219–228 (1999).

    Article  CAS  Google Scholar 

  16. Hellmuth, K. et al. Yeast Los1p has properties of an exportin-like nucleocytoplasmic transport factor for tRNA. Mol. Cell. Biol. 18, 6364–6386 (1998).

    Article  Google Scholar 

  17. Siniossoglou, S. et al. A novel complex of nucleoporins, which includes Sec13p and a Sec13p homolog, is essential for normal nuclear pores. Cell 84, 265–275 (1996).

    Article  CAS  Google Scholar 

  18. Luo, M.-J. et al. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature (this issue).

Download references

Acknowledgements

We are grateful to R. Grosschedl for GST–Aly, J. Braspenning for L20GST-NPL3, J. Beggs for prp4-1 and prp16-2 mutants, and D. Tollervey for the strain GAL10::ProtA-RRP41 (P118). We thank R. Reed and the members of the Reed lab for critical reading of the manuscript. E.H. was a recipient of grants from the Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie.

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Correspondence to Ed Hurt.

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Sträßer, K., Hurt, E. Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p. Nature 413, 648–652 (2001). https://doi.org/10.1038/35098113

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