Institut for Biomedicin

Lars Bolund

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

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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
OriginalsprogEngelsk
TidsskriftP L o S One
Vol/bind7
Nummer9
Sider (fra-til)e46251
Antal sider15
ISSN1932-6203
DOI
StatusUdgivet - 25 sep. 2012

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