FUS (gene)

FUS (Fused in Sarcoma), also known as FUS RNA binding protein or translocated in liposarcoma (TLS), is a gene that encodes the FUS protein in humans. This protein is involved in multiple aspects of DNA and RNA metabolism, including RNA splicing, RNA transport, and DNA repair. Mutations in the FUS gene have been associated with several neurodegenerative diseases, most notably amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), highlighting its importance in neuronal cell function and the maintenance of genomic integrity.

Function

The FUS protein is a member of the FET family of RNA-binding proteins, which also includes EWSR1 and TAF15. It is predominantly located in the nucleus of cells but can shuttle between the nucleus and the cytoplasm. FUS plays a critical role in the regulation of gene expression by binding to RNA and influencing RNA splicing, as well as being involved in the repair of damaged DNA. Its ability to bind to ribonucleic acids is facilitated by its RNA recognition motif (RRM) and multiple arginine-glycine-glycine (RGG) boxes.

Clinical Significance

1. 1. 1. ALS and FTLD ###

Mutations in the FUS gene are linked to familial forms of amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease that leads to progressive weakness and eventually death due to respiratory failure. These mutations are also associated with frontotemporal lobar degeneration (FTLD), a type of dementia characterized by progressive neuronal loss in the frontal and temporal lobes of the brain. The exact mechanism by which FUS mutations lead to these diseases is not fully understood, but it is believed that the mutations disrupt normal FUS protein function, including RNA processing and transport, leading to neuronal dysfunction and death.

1. 1. 1. Other Diseases ###

Beyond ALS and FTLD, abnormalities in FUS have been implicated in other conditions, including certain types of cancer. In particular, FUS is known to be involved in chromosomal translocations in liposarcomas, where it fuses with the CHOP gene, leading to the production of an oncogenic fusion protein that contributes to cancer development.

Genetics

The FUS gene is located on the long (q) arm of chromosome 16 at position 24.1, designated as 16q24.1. Mutations in this gene can be inherited in an autosomal dominant manner, meaning that only one copy of the altered gene is sufficient to increase the risk of developing disease. However, sporadic cases of diseases associated with FUS mutations, where there is no family history of the disease, are also common.

Research Directions

Research into the FUS gene and its protein product continues to be a vibrant field, with studies aiming to unravel the complex roles of FUS in cellular metabolism and its contribution to disease. Efforts are underway to develop targeted therapies that can mitigate the effects of FUS mutations in ALS, FTLD, and other conditions. Understanding the molecular mechanisms by which FUS contributes to disease may lead to novel therapeutic strategies for these currently incurable conditions.