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Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

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Listed:
  • Katannya Kapeli

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Gabriel A. Pratt

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego
    University of California at San Diego)

  • Anthony Q. Vu

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • Kasey R. Hutt

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • Fernando J. Martinez

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • Balaji Sundararaman

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • Ranjan Batra

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego
    University of California at San Diego)

  • Peter Freese

    (MIT)

  • Nicole J. Lambert

    (MIT)

  • Stephanie C. Huelga

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego
    University of California at San Diego)

  • Seung J. Chun

    (Ionis Pharmaceuticals)

  • Tiffany Y. Liang

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • Jeremy Chang

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego)

  • John P. Donohue

    (Cell and Developmental Biology, Sinsheimer Labs, University of California)

  • Lily Shiue

    (Cell and Developmental Biology, Sinsheimer Labs, University of California)

  • Jiayu Zhang

    (College of Medicine, University of Kentucky)

  • Haining Zhu

    (College of Medicine, University of Kentucky)

  • Franca Cambi

    (University of Kentucky)

  • Edward Kasarskis

    (University of Kentucky)

  • Shawn Hoon

    (Molecular Engineering Laboratory, A*STAR)

  • Manuel Ares Jr.

    (Cell and Developmental Biology, Sinsheimer Labs, University of California)

  • Christopher B. Burge

    (MIT)

  • John Ravits

    (University of California at San Diego)

  • Frank Rigo

    (Ionis Pharmaceuticals)

  • Gene W. Yeo

    (University of California at San Diego
    Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego
    Yong Loo Lin School of Medicine, National University of Singapore
    University of California at San Diego)

Abstract

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3′ untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

Suggested Citation

  • Katannya Kapeli & Gabriel A. Pratt & Anthony Q. Vu & Kasey R. Hutt & Fernando J. Martinez & Balaji Sundararaman & Ranjan Batra & Peter Freese & Nicole J. Lambert & Stephanie C. Huelga & Seung J. Chun , 2016. "Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12143
    DOI: 10.1038/ncomms12143
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    Cited by:

    1. Richard Taylor & Fursham Hamid & Triona Fielding & Patricia M. Gordon & Megan Maloney & Eugene V. Makeyev & Corinne Houart, 2022. "Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Oliver J. Ziff & Jacob Neeves & Jamie Mitchell & Giulia Tyzack & Carlos Martinez-Ruiz & Raphaelle Luisier & Anob M. Chakrabarti & Nicholas McGranahan & Kevin Litchfield & Simon J. Boulton & Ammar Al-C, 2023. "Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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