Fused in sarcoma messenger RNA (FUS mRNA) (FUS mRNA)

The Fused in sarcoma messenger RNA (FUS mRNA) transcript is the genetic template for the FUS protein, a multifunctional RNA-binding protein involved in transcription, splicing, and RNA transport (UniProt P35637) [1]. Mutations in the FUS gene are a significant cause of early-onset, aggressive forms of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), where the resulting protein mislocalizes to the cytoplasm and forms toxic aggregates (NIH) [2]. The FUS mRNA transcript has emerged as a primary therapeutic target for these conditions through the use of antisense oligonucleotides (ASOs). Drugs such as Jacifusen (ION363) are designed to bind specifically to the FUS mRNA and trigger its degradation via RNase H1 recruitment, thereby reducing the production of the toxic protein (Nature Medicine, 2022) [3]. This precision medicine approach aims to lower the overall proteotoxic burden in motor neurons and potentially slow the progression of neurodegeneration in patients harboring FUS mutations (ClinicalTrials.gov: NCT04768972) [4].

Other names

TLS mRNATranslocated in liposarcoma mRNAFUS/TLS mRNAFused in sarcoma transcriptPOMP75 mRNAHNRNPP2 mRNA

Antisense oligonucleotide-mediated degradation of the mRNA transcript via RNase H1 recruitment, preventing the translation of the FUS protein.