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

Open access
Kapeli, Katannya, Pratt, Gabriel A., Vu, Anthony Q., Hutt, Kasey R., Martinez, Fernando J., Sundararaman, Balaji, Batra, Ranjan, Freese, Peter, Lambert, Nicole J., Huelga, Stephanie C., Chun, Seung J., Liang, Tiffany Y., Chang, Jeremy, Donohue, John P., Shiue, Lily, Zhang, Jiayu, Zhu, Haining, Cambi, Franca, Kasarskis, Edward, Hoon, Shawn, Ares, Manuel, Burge, Christopher B., Ravits, John, Rigo, Frank, Yeo, Gene W.·2016·Nature Communications

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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Metadata

Authors
Kapeli, K., Pratt, G. A., Vu, A. Q., Hutt, K. R., Martinez, F. J., Sundararaman, B., Batra, R., Freese, P., Lambert, N. J., Huelga, S. C., Chun, S. J., Liang, T. Y., Chang, J., Donohue, J. P., Shiue, L., Zhang, J., Zhu, H., Cambi, F., Kasarskis, E., Hoon, S., Ares, M., Burge, C. B., Ravits, J., Rigo, F., & Yeo, G. W.
Venue
Nature Communications
Published
2016-07-05
Volume
7
Issue
1
Pages
12143-12143
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2465057958
Cited by
166
References
15
FWCI
11.16
Type
journal article
Language
en
Open access
gold

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The paper
Kapeli, K., Pratt, G. A., Vu, A. Q., Hutt, K. R., Martinez, F. J., Sundararaman, B., Batra, R., Freese, P., Lambert, N. J., Huelga, S. C., Chun, S. J., Liang, T. Y., Chang, J., Donohue, J. P., Shiue, L., Zhang, J., Zhu, H., Cambi, F., Kasarskis, E., . . . Yeo, G. W. (2016). Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. Nature Communications. https://doi.org/10.1038/ncomms12143

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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