Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses
Year: 2016
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms12143
Authors: 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, Tiffany Y. Liang, Jeremy Chang, John P. Donohue, Lily Shiue, Jiayu Zhang, Haining Zhu, Franca Cambi, Edward Kasarskis, Shawn Hoon, Manuel Ares, Christopher B. Burge, John Ravits, Frank Rigo, Gene W. Yeo
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, California Institute for Regenerative Medicine, ALS Association, California Institute of Regenerative Medicine, Ionis Pharmaceuticals, National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2465057958