Skip to main content

Thank you for visiting 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.

TDP-43 toxicity and the usefulness of junk

A new study shows that loss of the lariat debranching enzyme Dbr1 suppresses TDP-43 toxicity. The accumulated intronic lariat RNAs, which are normally degraded after splicing, likely act as decoys to sequester TDP-43 away from binding to and disrupting functions of other RNAs.

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

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Model for suppression of TDP-43 toxicity following loss of Dbr1.


  1. Arai, T. et al. Biochem. Biophys. Res. Commun. 351, 602–611 (2006).

    Article  CAS  Google Scholar 

  2. Neumann, M. et al. Science 314, 130–133 (2006).

    CAS  Google Scholar 

  3. Lagier-Tourenne, C., Polymenidou, M. & Cleveland, D.W. Hum. Mol. Genet. 19, R46–R64 (2010).

    Article  CAS  Google Scholar 

  4. Mackenzie, I.R., Rademakers, R. & Neumann, M. Lancet Neurol. 9, 995–1007 (2010).

    Article  CAS  Google Scholar 

  5. Armakola, M. et al. Nat. Genet. 44, 1302–1309 (2012).

    Article  CAS  Google Scholar 

  6. Elden, A.C. et al. Nature 466, 1069–1075 (2010).

    Article  CAS  Google Scholar 

  7. Arenas, J. & Hurwitz, J. J. Biol. Chem. 262, 4274–4279 (1987).

    CAS  PubMed  Google Scholar 

  8. Chapman, K.B. & Boeke, J.D. Cell 65, 483–492 (1991).

    Article  CAS  Google Scholar 

  9. Polymenidou, M. et al. Nat. Neurosci. 14, 459–468 (2011).

    Article  CAS  Google Scholar 

  10. Tollervey, J.R. et al. Nat. Neurosci. 14, 452–458 (2011).

    Article  CAS  Google Scholar 

  11. Sephton, C.F. et al. J. Biol. Chem. 286, 1204–1215 (2011).

    Article  CAS  Google Scholar 

  12. Xiao, S. et al. Mol. Cell. Neurosci. 47, 167–180 (2011).

    Article  CAS  Google Scholar 

  13. Buratti, E., Brindisi, A., Pagani, F. & Baralle, F.E. Am. J. Hum. Genet. 74, 1322–1325 (2004).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Don W Cleveland.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sun, S., Cleveland, D. TDP-43 toxicity and the usefulness of junk. Nat Genet 44, 1289–1291 (2012).

Download citation

  • Published:

  • Issue Date:

  • DOI:


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