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.
Blechingberg J[1], Luo Y, Bolund L, Damgaard CK, Nielsen AL
Affiliations
PMID: 23049996DOI: 10.1371/journal.pone.0046251
Impact factor: 3.752
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.
MeSH terms
Blotting, Western; Cell Line; Cytoplasmic Granules; Humans; Oxidative Stress; Polymerase Chain Reaction; RNA-Binding Protein EWS; RNA-Binding Protein FUS; TATA-Binding Protein Associated Factors
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