Esrp1 and Esrp2 regulate the stability of / mRNAs in zebrafish sensory hair cells.

RNA-binding proteins (RBPs) are important for post-transcriptional RNA processing, including pre-mRNA alternative splicing, mRNA stability, and translation. Several RBPs have been shown to play pivotal roles in the inner ear, whose dysfunction leads to auditory and/or balance impairments. Epithelial splicing-regulatory protein 1 (ESRP1) regulates alternative splicing and mRNA stability, and mutations in gene have been associated with sensorineural hearing loss in humans. In knockout mouse embryos, alternative splicing of its target genes such as is impaired, which eventually result in cochlear development deficits. However, knockout mice die soon after birth because of complications from cleft-lip and palate defects, impeding further investigations at later postnatal ages. In the present study, we explored the role of ESRP1 in hearing using zebrafish as a model. We showed that and its paralog are expressed in the inner ear and certain anterior lateral line (ALL) neuromasts. Furthermore, our data suggested that Esrp1 and Esrp2 are required for the mechano-electrical transduction (MET) function of hair cells. RNA sequencing results indicated a significant decrease in the levels of several mRNAs in double knockout larvae. Among the dysregulated genes are and , which encode essential subunits of the MET complex. Further investigations demonstrated that Esrp1/2 could directly bind to and mRNAs and affect their stability. Taken together, we showed here that Esrp1 and Esrp2 regulate the MET function of zebrafish sensory hair cells by modulating the stability of and mRNAs. ESRP1 is an important RNA-binding protein, whose malfunction has been associated with hearing loss in humans. knockout affects alternative splicing of its target mRNAs such as eventually leading to cochlear development deficits in mice. However, knockout mice die soon after birth, precluding further investigations at later postnatal ages. In this study, we explored the role of ESRP1 in hearing using zebrafish as a model. Our results demonstrated that and its paralog are expressed in the zebrafish inner ear, and that / double knockout compromised the mechano-electrical transduction (MET) function of hair cells. Additionally, we successfully identified and mRNAs as the targets of Esrp1/2, which encode essential subunits of the MET complex.