Tissue-specific alternative splicing (AS) is emerging as one of the most exciting types of mechanisms associated with organ development and disease. In the auditory system, many hearing-related genes undergo AS, and errors in this process result in syndromic or non-syndromic hearing loss. However, little is known about the factors and mechanisms directing AS in the inner ear. In the present study, we identified a novel RNA binding protein, Rbm24, which was critically involved in regulating inner-ear-specific AS. Rbm24 deletion resulted in hearing loss and defects in motor coordination. Global splicing analysis showed Rbm24 was required for correct splicing of a subset of pre-mRNA transcripts with essential roles in stereocilia integrity and survival of hair cells. Furthermore, we identified that Rbm24 directly regulated the splicing of Cdh23, a known disease gene responsible for human Usher syndrome 1D and non-syndromic autosomal recessive deafness DFNB12. In conclusion, our findings demonstrated that Rbm24 was a critical factor in regulating inner-ear-specific splicing and maintaining the hearing and motor coordination function of the inner ear. Our data not only offer mechanistic insights but also provide functional annotation of Rbm24 splicing targets that contribute to hearing loss.

组织特异性替代剪接（AS）成为与器官发育和疾病相关的最令人兴奋的机制之一。在听觉系统中，许多与听力相关的基因都经历了AS，并且此过程中的错误导致综合征性或非综合征性听力损失。然而，对于引导AS进入内耳的因素和机制知之甚少。在本研究中，我们确定了一种新型的RNA结合蛋白Rbm24，该蛋白与调节内耳特异性AS至关重要。Rbm24缺失导致听力损失和运动协调障碍。全球剪接分析表明，Rbm24是正确剪接一部分pre-mRNA转录本所必需的，而子转录本在立体纤毛完整性和毛细胞存活中起着重要作用。此外，我们发现Rbm24直接调节了Cdh23的剪接，一个已知的疾病基因，可导致人类Usher综合征1D和非综合征性常染色体隐性遗传性耳聋DFNB12。总之，我们的发现表明Rbm24是调节内耳特异性剪接并维持内耳的听力和运动协调功能的关键因素。我们的数据不仅提供了机械方面的见解，而且还提供了有助于听力损失的Rbm24剪接靶标的功能注释。