Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Quality control of mRNA 3′-end processing is linked to the nuclear exosome

Abstract

An emerging theme in messenger RNA metabolism is the coupling of nuclear pre-mRNA processing events, which contributes to mRNA quality control1. Most eukaryotic mRNAs acquire a poly(A) tail during 3′-end processing within the nucleus, and this is coupled to efficient export of mRNAs to the cytoplasm2,3. In the yeast Saccharomyces cerevisiae, a common consequence of defective nuclear export of mRNA is the hyperadenylation of nascent transcripts4,5, which are sequestered at or near their sites of transcription5. This implies that polyadenylation and nuclear export are coupled in a step that involves the release of mRNA from transcription site foci. Here we demonstrate that transcripts which fail to acquire a poly(A) tail are also retained at or near transcription sites. Surprisingly, this retention mechanism requires the protein Rrp6p and the nuclear exosome, a large complex of exonucleolytic enzymes6,7. In exosome mutants, hypo- as well as hyperadenylated mRNAs are released and translated. These observations suggest that the exosome contributes to a checkpoint that monitors proper 3′-end formation of mRNA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: SSA4 poly(A)- mRNA accumulates in an intranuclear focus in an Rrp6p-dependent manner.
Figure 2: Rrp6p mediates transcription site foci retention of HSP104 and SSA4 mRNAs in mRNA export mutants.
Figure 3: Lesions in the nuclear exosome alter the distribution of mRNA in the rat7-1 background.

Similar content being viewed by others

References

  1. Maquat, L. E. & Carmichael, G. G. Quality control of mRNA function. Cell 104, 173–176 (2001).

    Article  CAS  Google Scholar 

  2. Eckner, R., Ellmeier, W. & Birnstiel, M. L. Mature mRNA 3′ end formation stimulates RNA export from the nucleus. EMBO J. 10, 3513–3522 (1991).

    Article  CAS  Google Scholar 

  3. Huang, Y. & Carmichael, G. C. Role of polyadenylation in nucleocytoplasmic transport of mRNA. Mol. Cell. Biol. 16, 1534–1542 (1996).

    Article  CAS  Google Scholar 

  4. Hilleren, P. & Parker, R. Defects in mRNA export factors Rat7p, Gle1p, Mex67p and Rat8p cause hyperadenylation during 3′ end formation of nascent transcripts. RNA 7, 753–764 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Briggs, M. W., Burkard, K. T. & Butler, J. S. Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3′ end formation. J. Biol. Chem. 273, 13255–13263 (1998).

    Article  CAS  Google Scholar 

  7. Mitchell, P., Petfalski, E., Shevchenko, A., Mann, M. & Tollervey, D. The exosome: A conserved eukaryotic RNA processing complex containing multiple 3′→5′ exoribonucleases. Cell 91, 457–466 (1997).

    Article  CAS  Google Scholar 

  8. Patel, D. & Butler, J. S. Conditional defect in mRNA 3′ end processing caused by a mutation in the gene for poly(A) polymerase. Mol. Cell. Biol. 12, 3297–3304 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Burkard, K. T. & Butler, J. S. A nuclear 3′-5′ exonuclease involved in mRNA degradation interacts with poly(A) polymerase and the hnRNA protein Npl3p. Mol. Cell. Biol. 20, 604–616 (2000).

    Article  CAS  Google Scholar 

  10. Decker, C. J. & Parker, R. A turnover pathway for both stable and unstable mRNAs in yeast: Evidence for a requirement for deadenylation. Genes Dev. 7, 1632–1643 (1993).

    Article  CAS  Google Scholar 

  11. Allmang, C. et al. Functions of the exosome in rRNA, snoRNA and snRNA synthesis. EMBO J. 18, 5399–5410 (1999).

    Article  CAS  Google Scholar 

  12. van Hoof, A., Lennertz, P. & Parker, R. Yeast exosome mutants accumulate 3′-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol. Cell. Biol. 20, 441–452 (2000).

    Article  CAS  Google Scholar 

  13. 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 

  14. Gorsch, L. C., Dockendorff, T. C. & Cole, C. N. A conditional allele of the novel repeat-containing yeast nucleoporin RAT7/NUP159 causes both rapid cessation of mRNA export and reversible clustering of nuclear pore complexes. J. Cell Biol. 129, 939–955 (1995).

    Article  CAS  Google Scholar 

  15. Lee, M. S., Henry, M. & Silver, P. A. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. Genes Dev. 10, 1233–1246 (1996).

    Article  CAS  Google Scholar 

  16. Vainberg, I. E., Dower, K. & Rosbash, M. Nuclear export of heat shock and non-heat-shock mRNA occurs via similar pathways. Mol. Cell. Biol. 20, 3996–4005 (2000).

    Article  CAS  Google Scholar 

  17. Mandart, E. & Parker, R. Effects of mutations in the Saccharomyces cerevisiae RNA14, RNA15, and PAP1 genes on polyadenylation in vivo. Mol. Cell. Biol. 15, 6979–6986 (1995).

    Article  CAS  Google Scholar 

  18. Amrani, N., Dufour, M. E., Bonneaud, N. & Lacroute, F. Mutations in STS1 suppress the defect in 3′ mRNA processing caused by the rna15-2 mutation in Saccharomyces cerevisiae. Mol. Gen. Genet. 252, 552–562 (1996).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank I. Mattaj for critically reading the manuscript. This work was supported by the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roy Parker.

Supplementary information

Supplementary Table1. Yeast strains used in this study

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hilleren, P., McCarthy, T., Rosbash, M. et al. Quality control of mRNA 3′-end processing is linked to the nuclear exosome. Nature 413, 538–542 (2001). https://doi.org/10.1038/35097110

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35097110

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing