Alternative splice variants of the USH3A gene Clarin 1 (CLRN1)

Abstract

Clarin 1 (CLRN1) is a four-transmembrane protein expressed in cochlear hair cells and neural retina, and when mutated it causes Usher syndrome type 3 (USH3). The main human splice variant of CLRN1 is composed of three exons that code for a 232-aa protein. In this study, we aimed to refine the structure of CLRN1 by an examination of transcript splice variants and promoter regions. Analysis of human retinal cDNA revealed 11 CLRN1 splice variants, of which 5 have not been previously reported. We studied the regulation of gene expression by several promoter domains using a luciferase assay, and identified 1000 nt upstream of the translation start site of the primary CLRN1 splice variant as the principal promoter region. Our results suggest that the CLRN1 gene is significantly more complex than previously described. The complexity of the CLRN1 gene and the identification of multiple splice variants may partially explain why mutations in CLRN1 result in substantial variation in clinical phenotype.

A novel 5-bp deletion in Clarin 1 in a family with Usher syndrome

“…Several CLRN1 splice isoforms have been described with the main one being formed by three exons, named 0, 2, and 3, encoding a 232 amino acid protein. [6][7][8] CLRN1 belongs to a large family of transmembrane proteins including both the tetraspanin and the claudin families. Members of this family have several roles including regulating cell morphology, motility, invasion, fusion, and signaling.…”

Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome

“…1, 2, and Figure 1A). CLRN1 transcripts predict several isoforms (3). At least 3 splice isoforms have been reported; reverse transcriptase PCR (RT-PCR) and Western blots on the inner ear and eye revealed the expression of isoforms 2 (containing exons 1, 3, and 4) and 3 (containing exons 1 and 4) ( Figure 1, A and B).…”

Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies

“…Like other USH genes, clarin-1 has multiple transcript variants due to different splicings and usages of transcription start sites (Vastinsalo et al, 2010). The primary transcript encodes a protein with four predicted transmembrane domains and a C-terminal potential PBM (Figure 3).…”