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.

  • Brief Communication
  • Published:

Large-scale mapping of branchpoints in human pre-mRNA transcripts in vivo

Nature Structural & Molecular Biology volume 19, pages 719–721 (2012)Cite this article

Subjects

Abstract

We present the first large-scale identification of lariats—the transient branched introns that are released as a byproduct of pre-mRNA splicing. The locations of the branchpoints in these introns provide insight into the early steps of splicing. From this data set, we have developed a comprehensive model of 3′ splice-site selection, identified new mechanisms of alternative splicing and mapped the distribution of splicing factors around branchpoints.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Identifying pre-mRNA lariats in human transcripts.
Figure 2: CLIP-tag density of splicing factors relative to the closest branchpoint.

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Vogel, J., Hess, W.R. & Borner, T. Nucleic Acids Res. 25, 2030–2031 (1997).

    Article  CAS  Google Scholar 

  2. Parkinson, H. et al. Nucleic Acids Res. 37, D868–D872 (2009).

    Article  CAS  Google Scholar 

  3. Stenson, P.D. et al. Hum. Mutat. 21, 577–581 (2003).

    Article  CAS  Google Scholar 

  4. Legrain, P., Seraphin, B. & Rosbash, M. Mol. Cell. Biol. 8, 3755–3760 (1988).

    Article  CAS  Google Scholar 

  5. Smith, C.W., Porro, E.B., Patton, J.G. & Nadal-Ginard, B. Nature 342, 243–247 (1989).

    Article  CAS  Google Scholar 

  6. Gooding, C. et al. Genome Biol. 7, R1 (2006).

    Article  Google Scholar 

  7. Chen, S., Anderson, K. & Moore, M.J. Proc. Natl. Acad. Sci. USA 97, 593–598 (2000).

    Article  CAS  Google Scholar 

  8. Chua, K. & Reed, R. Mol. Cell. Biol. 21, 1509–1514 (2001).

    Article  CAS  Google Scholar 

  9. Meyer, M., Plass, M., Perez-Valle, J., Eyras, E. & Vilardell, J. Mol. Cell 43, 1033–1039 (2011).

    Article  CAS  Google Scholar 

  10. Smith, C.W.J., Chu, T.T. & Nadalginard, B. Mol. Cell. Biol. 13, 4939–4952 (1993).

    Article  CAS  Google Scholar 

  11. Quinlan, R. Mach. Learn. 1, 81–106 (1986).

    Google Scholar 

  12. König, J. et al. Nat. Struct. Mol. Biol. 17, 909–915 (2010).

    Article  Google Scholar 

  13. Xue, Y. et al. Mol. Cell 36, 996–1006 (2009).

    Article  CAS  Google Scholar 

  14. Yeo, G.W. et al. Nat. Struct. Mol. Biol. 16, 130–137 (2009).

    Article  CAS  Google Scholar 

  15. Huelga, S.C. et al. Cell Reports 1, 167–178 (2012).

    Article  CAS  Google Scholar 

  16. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S.L. Genome Biol. 10, R25 (2009).

    Article  Google Scholar 

  17. Hertz, G.Z. & Stormo, G.D. Bioinformatics 15, 563–577 (1999).

    Article  CAS  Google Scholar 

  18. Chenna, R. et al. Nucleic Acids Res. 31, 3497–3500 (2003).

    Article  CAS  Google Scholar 

  19. Crooks, G.E., Hon, G., Chandonia, J.M. & Brenner, S.E. Genome Res. 14, 1188–1190 (2004).

    Article  CAS  Google Scholar 

  20. Trapnell, C., Pachter, L. & Salzberg, S.L. Bioinformatics 25, 1105–1111 (2009).

    Article  CAS  Google Scholar 

  21. Ding, Y., Chan, C.Y. & Lawrence, C.E. Nucleic Acids Res. 32, W135–W141 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank R. Freiman and members of the Fairbrother lab for useful comments, suggestions and assistance; G. Schroth and Illumina for sharing body-map sequencing data; and G. Yeo for sharing RNA binding data before publication. The lab was supported by US federal funding sources R01GM095612–01 and NSF1020552 (both to A.J.T., W.G.F., J.S.S.) and by Brown University through the use of the OSCAR cluster (administered by the Center for Computation and Visualization) and the genomics core facility (8P30GM103410).

Author information

Author notes

  1. Allison J Taggart and Alec M DeSimone: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology, Laboratory of Molecular Medicine, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, USA

    Allison J Taggart, Alec M DeSimone, Madeleine E Filloux & William G Fairbrother

  2. Center for Biomedical Engineering, Brown University, Providence, Rhode Island, USA

    Allison J Taggart & William G Fairbrother

  3. Department of Molecular Microbiology and Immunology, Laboratory of Molecular Medicine, Brown University, Providence, Rhode Island, USA

    Janice S Shih & William G Fairbrother

  4. Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, USA

    William G Fairbrother

Authors
  1. Allison J Taggart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alec M DeSimone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janice S Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madeleine E Filloux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William G Fairbrother
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.J.T. and W.G.F conceived and planned the project. A.J.T., A.M.D., J.S.S. and M.E.F collected data. A.J.T., A.M.D., J.S.S. and M.E.F performed analysis. A.J.T., A.M.D., J.S.S. and W.G.F. wrote the paper.

Corresponding author

Correspondence to William G Fairbrother.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 and Supplementary Tables 1 and 2 (PDF 1930 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taggart, A., DeSimone, A., Shih, J. et al. Large-scale mapping of branchpoints in human pre-mRNA transcripts in vivo. Nat Struct Mol Biol 19, 719–721 (2012). https://doi.org/10.1038/nsmb.2327

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.2327

This article is cited by

Search

Advanced 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