Abstract
BackgroundFUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types.ResultsFUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells.ConclusionOur results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.
Highlights
FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias
Gene expression was for a long time considered to consist of a chain of distinct events starting with synthesis of RNA, followed by splicing and ending with mature mRNAs being translated in the cytoplasm
FET proteins were not detected in melanocytes and cardiac muscle cells and neither FUS nor TAF15 were detected in cardiac endothelium
Summary
FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. The discovery of multifunctional RNA-binding proteins has since joined transcription, RNA processing, transport of RNA species and translation into an integrated tightly regulated cellular machinery [1,2] One such group of proteins is the FET (previously called TET) family of RNA-binding proteins [3]. The 5' parts of the human FET genes are as a result of chromosomal translocations rearranged and fused to various transcription factor genes in multiple human malignancies These events are considered the driving forces of cancer development in their associated diseases [2,10]
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