Usher syndrome type 2A pre-messenger RNA (USH2A pre-mRNA) (USH2A pre-mRNA)

Usher syndrome type 2A pre-messenger RNA (USH2A pre-mRNA) is the transcript of the USH2A gene, which encodes the usherin protein. Usherin is an essential transmembrane component of the basement membrane in the inner ear and retina, playing a critical role in the maintenance of photoreceptor cells and the development of cochlear hair cell stereocilia [1, 4]. Mutations in the USH2A pre-mRNA, particularly those involving exon 13, often lead to the production of a truncated or non-functional protein, causing Usher syndrome type 2A (characterized by congenital hearing loss and progressive retinitis pigmentosa) or nonsyndromic retinitis pigmentosa [1, 2, 5]. This pre-mRNA is a significant therapeutic target for antisense oligonucleotides (ASOs), which are designed to modulate splicing [7, 9]. Because the USH2A gene is too large for conventional viral-mediated gene therapy, ASOs like ultevursen target the pre-mRNA to induce exon skipping [3, 6]. By masking specific sequences in exon 13, these drugs allow the cellular machinery to bypass the mutation-bearing exon and restore the open reading frame. This results in the synthesis of a shortened but functional usherin protein, which aims to preserve retinal function and slow the progression of vision loss in affected individuals [7, 10, 16].

Other names

Usherin pre-messenger RNAUSH2A pre-messenger RNAUsherin pre-mRNAUSH2A precursor mRNA

Antisense oligonucleotide-mediated exon skipping to restore the open reading frame and produce a functional, shortened usherin protein [3, 7].