Usher syndrome type 2A pre-messenger RNA exon 13 region (USH2A pre-mRNA exon 13) (USH2A pre-mRNA exon 13)

The Usher syndrome type 2A (USH2A) pre-messenger RNA exon 13 region is a critical segment of the USH2A transcript that encodes a portion of the usherin protein. Usherin is a large basement membrane-like protein located in the connecting cilia of photoreceptors and the hair cell bundle of the inner ear, where it is vital for structural integrity and sensory function (UniProt: O75445). Mutations in exon 13, most notably the c.2299delG frameshift mutation, are among the most frequent causes of Usher syndrome type 2A and autosomal recessive retinitis pigmentosa (NCBI Gene: 7399). This specific RNA region is targeted by antisense oligonucleotides (ASOs) like ulrevorsen (QR-421a) to modulate the splicing process. These therapeutic agents bind to the pre-mRNA and mask the splice sites of exon 13, causing the cellular machinery to skip this exon (Dulla et al., 2021, Molecular Therapy - Nucleic Acids). Because exon 13 contains an even number of nucleotides, its removal maintains the reading frame, leading to the production of a shortened but functional usherin protein that can mitigate the degenerative effects of the disease.

Other names

USH2A exon 13Usherin pre-mRNA exon 13USH2A pre-messenger RNA exon 13

Antisense oligonucleotide-mediated exon skipping to exclude the mutation-bearing exon 13 from the mature mRNA, restoring the reading frame and producing a functional truncated usherin protein.