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Gene Expression Responses to FUS, EWS, and TAF15 Reduction and Stress Granule Sequestration Analyses Identifies FET-Protein Non-Redundant Functions

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
9
Identifiers
DOI: 10.1371/journal.pone.0046251
Keywords
  • Research Article
  • Biology
  • Biochemistry
  • Nucleic Acids
  • Rna
  • Rna Interference
  • Genetics
  • Gene Expression
  • Dna Transcription
  • Rna Processing
  • Molecular Genetics
  • Gene Regulation
  • Gene Function
  • Genetics Of Disease
  • Molecular Cell Biology
  • Signal Transduction
  • Signaling Cascades
  • Stress Signaling Cascade
  • Cellular Stress Responses
  • Neuroscience
  • Molecular Neuroscience
  • Signaling Pathways
  • Cellular Neuroscience
  • Neurobiology Of Disease And Regeneration
Disciplines
  • Biology
  • Medicine

Abstract

The FET family of proteins is composed of FUS/TLS, EWS/EWSR1, and TAF15 and possesses RNA- and DNA-binding capacities. The FET-proteins are involved in transcriptional regulation and RNA processing, and FET-gene deregulation is associated with development of cancer and protein granule formations in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and trinucleotide repeat expansion diseases. We here describe a comparative characterization of FET-protein localization and gene regulatory functions. We show that FUS and TAF15 locate to cellular stress granules to a larger extend than EWS. FET-proteins have no major importance for stress granule formation and cellular stress responses, indicating that FET-protein stress granule association most likely is a downstream response to cellular stress. Gene expression analyses showed that the cellular response towards FUS and TAF15 reduction is relatively similar whereas EWS reduction resulted in a more unique response. The presented data support that FUS and TAF15 are more functionally related to each other, and that the FET-proteins have distinct functions in cellular signaling pathways which could have implications for the neurological disease pathogenesis.

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