Transcriptomics

Dataset Information

237

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


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 CLIP-seq sample(s).

ORGANISM(S): Mus musculus  

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

PROVIDER: E-GEOD-77700 | ArrayExpress | 2016-07-05

SECONDARY ACCESSION(S): GSE77700SRP069786PRJNA311236

REPOSITORIES: GEO, ArrayExpress, ENA

Similar Datasets

2016-07-05 | E-GEOD-77702 | ArrayExpress
2016-07-05 | E-GEOD-77703 | ArrayExpress
2016-07-05 | E-GEOD-77704 | ArrayExpress
2016-07-05 | E-GEOD-77699 | ArrayExpress
2012-09-30 | E-GEOD-40653 | ArrayExpress
2012-09-30 | E-GEOD-40651 | ArrayExpress
2012-09-30 | E-GEOD-40652 | ArrayExpress
2012-09-30 | E-GEOD-40649 | ArrayExpress
2010-07-31 | GSE22351 | GEO
2010-07-30 | E-GEOD-22351 | ArrayExpress