Alternative splicing of inner-ear-expressed genes

Abstract

Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the α subunit of the Ca²⁺-activated K⁺ channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

Keywords

alternative splicing / inner ear / hearing loss / hair cells

References

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Acknowledgements

Our laboratory is supported by grants from the National Basic Research Program of China (No. 2013CB967700), the National Natural Science Foundation of China (Nos. 31401007 and 31371355), the China Postdoctoral Science Foundation (No. 2014M560550), and the Fundamental Research Funds of Shandong University (Nos. 2014HW011 and 2015JC027). The funders had no role in the preparation of the manuscript.

Compliance with ethics guidelines

Yanfei Wang, Yueyue Liu, Hongyun Nie, Xin Ma, and Zhigang Xu declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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