2. Academic Validation
  3. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses

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

  • Nat Commun. 2016 Jul 5:7:12143. doi: 10.1038/ncomms12143.
Katannya Kapeli 1 2 3,  Gabriel A Pratt 1 2 4,  Anthony Q Vu 1 2,  Kasey R Hutt 1 2,  Fernando J Martinez 1 2,  Balaji Sundararaman 1 2,  Ranjan Batra 1 2 5,  Peter Freese 6,  Nicole J Lambert 6,  Stephanie C Huelga 1 2 4,  Seung J Chun 7,  Tiffany Y Liang 1 2,  Jeremy Chang 1 2,  John P Donohue 8,  Lily Shiue 8,  Jiayu Zhang 9,  Haining Zhu 9,  Franca Cambi 10,  Edward Kasarskis 10,  Shawn Hoon 11,  Manuel Ares Jr 8,  Christopher B Burge 6,  John Ravits 5,  Frank Rigo 7,  Gene W Yeo 1 2 3 4 11
Affiliations

Affiliations

  • 1 Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.
  • 2 Stem Cell Program and Institute for Genomic Medicine, University of California at San Diego, La Jolla, California 92093, USA.
  • 3 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117549, Singapore.
  • 4 Department of Bioinformatics and Systems Biology, University of California at San Diego, La Jolla, California 92093, USA.
  • 5 Department of Neurosciences, University of California at San Diego, La Jolla, California 92093, USA.
  • 6 Department of Biology, MIT, Cambridge, Massachusetts 02142, USA.
  • 7 Ionis Pharmaceuticals, Carlsbad, California 92010, USA.
  • 8 Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, California 95064, USA.
  • 9 Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, USA.
  • 10 Department of Neurology, University of Kentucky, Lexington, Kentucky 40536, USA.
  • 11 Molecular Engineering Laboratory, A*STAR, Singapore 138673, Singapore.
PMID: 27378374 DOI: 10.1038/ncomms12143
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.

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