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 non-coding 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.

Keywords: Deafness; Hearing; Inner ear; LncRNA; Notch.

Figure 1.

Genomic characterization of lncRNA candidates

Figure 2.

Expression of lncRNAs in the inner ear

Figure 3.

Expression of lncRNA candidates in different cells types of the inner ear

Figure 4.

lncRNA sub-cellular localization

Figure 5.

lncRNA expression in a mouse tissue panel, using qRT-PCR