Dataset Information


Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array]

ABSTRACT: TDP-43, FUS, and TAF15 are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We integrate CLIP-seq and RNA Bind-N-Seq technologies to discover that TAF15 binds to ~4,900 RNAs enriched for GGUA motifs. In the mouse brain, TAF15 and FUS, but not TDP-43, exhibit strikingly similar RNA binding profiles, yet they alter the expression of distinct mRNA populations upon their individual depletions. TAF15 has a minimal role in alternative splicing and instead affects RNA turnover, consistent with an enrichment of TAF15 binding sites in 3’ untranslated regions. In human stem cell-derived motor neurons, loss of both TAF15 and FUS affected mRNAs distinct from those altered by loss of either protein alone, revealing redundant roles for TAF15 and FUS in maintaining mRNA levels. Furthermore, concomitant rather than individual depletion of TAF15 and FUS more closely resembles RNA profiles of motor neurons derived from FUS R521G ALS patients or from late-stage, sporadic ALS patients. Our study reveals convergent and divergent mechanisms by which FUS, TAF15 and TDP-43 affects RNA metabolism in neurological disease. RNA-seq, CLIP-seq and arrays in mouse and human against TAF15 knockdowns This Series represents array sample(s).

ORGANISM(S): Mus musculus  

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

PROVIDER: E-GEOD-77699 | ArrayExpress | 2016-07-05



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