Position Specific Alternative Splicing and Gene Expression Profiles Along the Tonotopic Axis of Chick Cochlea.

Heiyeun Koo,Hyeyoung Park,Juw Won Park,Sungbo Jung,Jae Yeon Hwang,Jinwoong Bok

doi:10.3389/fmolb.2021.726976

Heiyeun Koo, Hyeyoung Park + Show 4 more

Open Access

https://doi.org/10.3389/fmolb.2021.726976

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Abstract

Alternative splicing (AS) refers to the production of multiple mRNA isoforms from a single gene due to alternative selection of exons or splice sites during pre-mRNA splicing. It is a primary mechanism of gene regulation in higher eukaryotes and significantly expands the functional complexity of eukaryotic organisms, contributing to animal development and disease. Recent studies have shown that AS also influences functional diversity by affecting the transcriptomic and proteomic profiles in a position-dependent manner in a single organ. The peripheral hearing organ, the cochlea, is organized to detect sounds at different frequencies depending on its location along the longitudinal axis. This unique functional configuration, the tonotopy, is known to be facilitated by differential gene expression along the cochlear duct. We profiled transcriptome-wide gene expression and AS changes that occur within the different positions of chick cochlea. These analyses revealed distinct gene expression profiles and AS, including a splicing program that is unique to tonotopy. Changes in the expression of splicing factors PTBP3, ESRP1, and ESRP2 were demonstrated to contribute to position-specific AS. RNA-binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS at different positions by different RNA-binding proteins. These data, along with gene ontology (GO) analysis, represent a comprehensive analysis of the dynamic regulation of AS at different positions in chick cochlea.

Highlights

Alternative splicing (AS) refers to the production of multiple mRNA isoforms from a single gene due to alternative selection of exons or splice sites during pre-mRNA splicing
To evaluate phenotypes associated with different regions along the longitudinal axis of the cochlea duct, we extracted mRNA from three different regions of the chick cochlea, base, middle and apex, and performed an RNA-seq experiment
To assess position-specific gene expression that might be responsible for configuration and maintenance of the tonotopic axis of the cochlea duct, we identified differentially expressed genes on the three regions

Summary

Introduction

Alternative splicing (AS) refers to the production of multiple mRNA isoforms from a single gene due to alternative selection of exons or splice sites during pre-mRNA splicing. Previous studies have shown that AS may influence functional diversity by Alternative Splicing Along Tonotopic Axis affecting the transcriptomic and proteomic profiles in a positiondependent manner in a single organ (Navaratnam et al, 1997; Rosenblatt et al, 1997; Baralle and Giudice, 2017) Auditory sensory organs such as the organ of Corti in mammals and the basilar papilla in avians are responsible for receiving and relaying sound information from the environment to the brain. The hair cells located at the basal (proximal) regions of the cochlea are tuned to detect high frequencies of sounds, whereas the hair cells at the apical (distal) cochlear regions are tuned to lower frequencies This position-dependent frequency discrimination capability of the auditory system is known as the tonotopy. The length of the hair bundle, which are composed of tens of stereocilium arranged in a stair-case pattern, is shorter at the base and gradually longer toward the apex, whereas the width of hair bundle is wider at the base and gradually narrower toward the apex (Son et al, 2015; Moon et al, 2020)

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