RNA-binding protein EWS

RNA-binding protein EWS (EWSR1) is a 656-amino-acid RNA-binding protein that binds ssRNA containing the consensus sequence 5'-AGGUAA-3' and may function as a transcriptional repressor (UniProt: Q01844). It is a component of the transcription initiation machinery, and fusion proteins derived from EWSR1 can aberrantly activate target genes and disrupt normal gene expression.

UniProt documents EWSR1 primarily in the context of Ewing sarcoma and angiomatoid fibrous histiocytoma, both malignant tumors affecting children and adolescents. EWSR1 fusions in these cancers are thought to interfere with CTD-POLII function within the transcription complex.

In Alzheimer's disease, EWSR1 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics: mean log2FC −1.10, detected in one subcellular fraction from TMT-labeled proteomic analysis). The functional significance of this reduced expression in AD pathogenesis remains to be determined.