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RNA targets of wild-type and mutant FET family proteins

Nature Structural & Molecular Biology volume 18, pages 1428–1431 (2011)Cite this article

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Abstract

FUS, EWSR1 and TAF15, constituting the FET protein family, are abundant, highly conserved RNA-binding proteins with important roles in oncogenesis and neuronal disease, yet their RNA targets and recognition elements are unknown. Using PAR-CLIP, we defined global RNA targets for all human FET proteins and two ALS-causing human FUS mutants. FET members showed similar binding profiles, whereas FUS mutants showed a drastically altered binding pattern, consistent with changes in subcellular localization.

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Figure 1: Protein-RNA interaction maps of FET proteins.
Figure 2: RNA-binding preferences of wild-type FET and mutant FUS proteins.

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Acknowledgements

J.I.H. is supported by the Deutsche Forschungsgemeinschaft, E.L. is supported by the Swedish Research Council and M.H. is supported by the Charles Revson Jr. Foundation. T.T. is a Howard Hughes Medical Institute investigator, and work in his laboratory was supported by US National Institutes of Health grant MH08442 and by the Starr Foundation.

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Author notes

  1. Jessica I Hoell and Erik Larsson: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York, USA

    Jessica I Hoell, Simon Runge, Jeffrey D Nusbaum, Thalia A Farazi, Markus Hafner & Thomas Tuschl

  2. Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Heinrich Heine University, Duesseldorf, Germany

    Jessica I Hoell, Sujitha Duggimpudi & Arndt Borkhardt

  3. Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Erik Larsson & Chris Sander

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  1. Jessica I Hoell
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  4. Jeffrey D Nusbaum
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Contributions

J.I.H. carried out stable cell line generation (FUS, EWSR1 and FUS mutants), PAR-CLIP experiments (FUS, EWSR1 and FUS mutants), short interfering RNA (siRNA) knockdowns and gel shift experiments; E.L. did all the computational analyses; S.R. carried out the generation of TAF15 stable cell lines and the TAF15 PAR-CLIP; J.D.N. did the recombinant protein purification and conducted gel shift experiments; S.D. conducted the western blot experiments; T.A.F. and M.H. did the siRNA knockdowns; A.B., C.S. and T.T. supervised the project; and E.L., J.I.H. and T.T. wrote the paper.

Corresponding authors

Correspondence to Chris Sander or Thomas Tuschl.

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Competing interests

T.T. is cofounder and scientific advisor of Alnylam Pharmaceuticals and advisor to Regulus Therapeutics.

Supplementary information

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Supplementary Figures 1–6, Supplementary Tables 1–3 and Supplementary Methods (PDF 1226 kb)

Supplementary Data 1 (TXT 2931 kb)

Supplementary Data 2 (XLS 1660 kb)

Supplementary Data 3 (XLS 26 kb)

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Hoell, J., Larsson, E., Runge, S. et al. RNA targets of wild-type and mutant FET family proteins. Nat Struct Mol Biol 18, 1428–1431 (2011). https://doi.org/10.1038/nsmb.2163

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