Gene expression responses to FUS, EWS, and TAF15 reduction and stress granule sequestration analyses identifies FET-protein non-redundant functions

PLoS One. 2012;7(9):e46251. doi: 10.1371/journal.pone.0046251. Epub 2012 Sep 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cytoplasmic Granules / metabolism*
  • Humans
  • Oxidative Stress / physiology
  • Polymerase Chain Reaction
  • RNA-Binding Protein EWS / metabolism*
  • RNA-Binding Protein FUS / metabolism*
  • TATA-Binding Protein Associated Factors / metabolism*

Substances

  • RNA-Binding Protein EWS
  • RNA-Binding Protein FUS
  • TAF15 protein, human
  • TATA-Binding Protein Associated Factors

Grants and funding

This project was supported by a fellowship to JB by the Faculty of Health, Aarhus University, and supported by Fonden til Lægevidenskabens fremme, the Danish Research Council (FSS), and the Lundbeck Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.