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

Nature Structural & Molecular Biology volume 19, pages719–721(2012)Cite this article

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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.

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

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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).

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Author notes

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

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
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  2. Alec M DeSimone
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  3. Janice S Shih
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  4. Madeleine E Filloux
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  5. William G Fairbrother
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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.

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The authors declare no competing financial interests.

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

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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

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