Gene expression responses to FUS, EWS, and TAF15 reduction and stress granule sequestration analyses identifies FET-protein non-redundant functions.
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.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Jenny
J
Blechingberg
Yonglun
Y
Luo
Lars
L
Bolund
Christian Kroun
CK
Damgaard
Anders Lade
AL
Nielsen
D015153:Blotting, Western; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D016133:Polymerase Chain Reaction; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*
D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors