FUs

FUS, also known as fused in sarcoma, is a gene that encodes an RNA-binding protein involved in multiple aspects of RNA metabolism. It belongs to the FET family of RNA-binding proteins, together with EWSR1 and TAF15. The FUS protein contains an N-terminal transactivation domain, a low-complexity prion-like domain, an RNA-recognition motif, multiple arginine-glycine-glycine (RGG) repeats, a zinc finger domain, and a C-terminal nuclear localization signal. These features enable binding to DNA, RNA, and protein partners, supporting roles in transcription, RNA splicing, mRNA transport, and DNA repair. The protein normally localizes to the nucleus but can shuttle to the cytoplasm under stress, where it participates in stress granules.

Mutations or chromosomal translocations involving FUS are linked to disease. In neurodegenerative disease, FUS mutations or mislocalization contribute to certain forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia with FUS pathology. In oncology, chromosomal translocations can create fusion proteins such as FUS-CHOP (also called FUS-DDIT3) in myxoid liposarcoma, acting as an oncogenic driver.

The term “FUS” reflects the discovery of the FUS-CHOP fusion in sarcoma, and the gene is a member of the broader FET protein family. Researchers study FUS to understand RNA processing and genome integrity, as well as its role in disease.

See also: EWSR1; TAF15; FET protein family; amyotrophic lateral sclerosis; frontotemporal dementia; liposarcoma.