Fused in sarcoma (FUS) mRNA (FUS)

Fused in sarcoma (FUS) mRNA is the transcript of the FUS gene, which encodes a multifunctional RNA-binding protein (RBP) belonging to the FET family. The FUS protein plays critical roles in cellular processes such as RNA splicing, DNA repair, and the transport of mRNA to dendrites (UniProt P35637). In patients with specific genetic mutations, the FUS protein mislocalizes from the nucleus to the cytoplasm, where it forms toxic aggregates that are a hallmark of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) (PubMed: 20019282). As a therapeutic target, FUS mRNA is addressed using antisense oligonucleotides (ASOs) designed to bind the transcript and promote its degradation via RNase H-mediated cleavage. This approach aims to reduce the synthesis of the FUS protein, thereby mitigating the gain-of-toxic-function effects associated with its aggregation. A prominent example of this strategy is ION363 (Jacifusen), which is currently under clinical investigation for the treatment of FUS-mutated ALS (ClinicalTrials.gov: NCT04768972). Beyond neurodegeneration, FUS is also involved in chromosomal translocations that lead to the development of certain cancers, such as myxoid liposarcoma. Therapeutic development focusing on FUS RNA represents a precision medicine approach for rare, aggressive forms of motor neuron disease.

Other names

TLSTranslocated in liposarcomaFUS/TLShnRNP P2Fused in sarcoma RNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H recruitment to reduce the expression of toxic FUS protein.