Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses
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Distinct and shared.pdf
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Author(s)
Kapeli, Katannya
Pratt, Gabriel A.
Vu, Anthony Q.
Hutt, Kasey R.
Martinez, Fernando J.
Sundararaman, Balaji
Batra, Ranjan
Huelga, Stephanie C.
Chun, Seung J.
Liang, Tiffany Y.
Date Issued
July 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Kapeli, Katannya et al. “Distinct and Shared Functions of ALS-Associated Proteins TDP-43, FUS and TAF15 Revealed by Multisystem Analyses.” Nature Communications 7 (2016): 12143.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Center for Biological & Computational Learning
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/ncomms12143
