Identification and characterization of key long non-coding RNAs in the mouse cochlea

Abstract

The auditory system is a complex sensory network with an orchestrated multilayer regulatory programme governing its development and maintenance. Accumulating evidence has implicated long noncoding RNAs (lncRNAs) as important regulators in numerous systems, as well as in pathological pathways. However, their function in the auditory system has yet to be explored. Using a set of specific criteria, we selected four lncRNAs expressed in the mouse cochlea, which are conserved in the human transcriptome and are relevant for inner ear function. Bioinformatic characterization demonstrated a lack of coding potential and an absence of evolutionary conservation that represent properties commonly shared by their class members. RNAscope® analysis of the spatial and temporal expression profiles revealed specific localization to inner ear cells. Sub-cellular localization analysis presented a distinct pattern for each lncRNA and mouse tissue expression evaluation displayed a large variability in terms of level and location. Our findings establish the expression of specific lncRNAs in different cell types of the auditory system and present a potential pathway by which the lncRNA Gas5 acts in the inner ear. Studying lncRNAs and deciphering their functions may deepen our knowledge of inner ear physiology and morphology and may reveal the basis of as yet unresolved genetic hearing loss-related pathologies. Moreover, our experimental design may be employed as a reference for studying other inner ear-related lncRNAs, as well as lncRNAs expressed in other sensory systems.

Prkra Mutation Alters Long Noncoding RNA Expression During Embryonic External Ear Development

“…12 Studies have shown that specific lncRNAs can be expressed in different cell types of the auditory system, with distinct expression patterns and variation. 13 The human auricle is supported by ear cartilage. When the ear cartilage is dysplastic, it may lead to auricle deformities.…”

“…For example, lncRNAs generally exist in the sensory epithelial cells of the mouse inner ear during the development of the auditory system, thereby contributing to the regulation of the development of the auditory system 12. Studies have shown that specific lncRNAs can be expressed in different cell types of the auditory system, with distinct expression patterns and variation 13…”

A cell type–specific approach to elucidate the role of miR-96 in inner ear hair cells

“…LncRNAs, such as Lockd, Dlx1as, Emx2os, and Soxot, are of interest because they are located in unresolved deafness-associated loci (Ushakov et al, 2017). Additionally, recent studies have begun to hypothesize roles for some lncRNAs in the inner ear, including Gas5, which may regulate the Notch1 pathway (Koffler-Brill et al, 2021). miRNAs have specific spatiotemporal expression in the auditory and vestibular systems, with some having known roles in inner ear development and function (Friedman et al, 2009;Rudnicki et al, 2014;Mahmoudian-sani et al, 2017).…”

The Genomics of Auditory Function and Disease

“…A handful of studies have characterized the expression profiles of lncRNAs in the inner ear by using high-throughput sequencing technologies ( 83 , 105 , 147 , 164 , 176 ). Some inner-ear lncRNAs are also expressed in other systems, such as Malat1 , while others, such as Xloc_012867 , are novel lncRNAs that are apparently restricted to the inner ear ( 83 ).…”

“…A handful of studies have characterized the expression profiles of lncRNAs in the inner ear by using high-throughput sequencing technologies ( 83 , 105 , 147 , 164 , 176 ). Some inner-ear lncRNAs are also expressed in other systems, such as Malat1 , while others, such as Xloc_012867 , are novel lncRNAs that are apparently restricted to the inner ear ( 83 ). A study identified the lncRNA Rubie as a candidate for circling behavior in mice, as it is expressed in the cochlea at embryonic stages and is found in close proximity to Bmp4, potentially regulating it in cis ( 138 ).…”