Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1

Alternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelect...

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Main Authors: Nana Li, Haibo Du, Rui Ren, Yanfei Wang, Zhigang Xu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2020/8898811
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author Nana Li
Haibo Du
Rui Ren
Yanfei Wang
Zhigang Xu
author_facet Nana Li
Haibo Du
Rui Ren
Yanfei Wang
Zhigang Xu
author_sort Nana Li
collection DOAJ
description Alternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelectrical transduction (MET) in the hair cells. Cdh23 gene contains 69 exons, and exon 68 is subjected to alternative splicing. Exon 68 of the Cdh23 gene is spliced into its mRNA only in a few cell types including hair cells. The mechanism responsible for the alternative splicing of Cdh23 exon 68 remains elusive. In the present work, we performed a cell-based screening to look for splicing factors that regulate the splicing of Cdh23 exon 68. RBM24 and RBM38 were identified to enhance the inclusion of Cdh23 exon 68. The splicing of Cdh23 exon 68 is affected in Rbm24 knockdown or knockout cells. Moreover, we also found that PTBP1 inhibits the inclusion of Cdh23 exon 68. Taken together, we show here that alternative splicing of Cdh23 exon 68 is regulated by RBM24, RBM38, and PTBP1.
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spelling doaj-art-1c78dd6dd239450eb982dafa4593305a2025-02-03T06:04:37ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/88988118898811Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1Nana Li0Haibo Du1Rui Ren2Yanfei Wang3Zhigang Xu4Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong Province, ChinaShandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong Province, ChinaShandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong Province, ChinaShandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong Province, ChinaShandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong Province, ChinaAlternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelectrical transduction (MET) in the hair cells. Cdh23 gene contains 69 exons, and exon 68 is subjected to alternative splicing. Exon 68 of the Cdh23 gene is spliced into its mRNA only in a few cell types including hair cells. The mechanism responsible for the alternative splicing of Cdh23 exon 68 remains elusive. In the present work, we performed a cell-based screening to look for splicing factors that regulate the splicing of Cdh23 exon 68. RBM24 and RBM38 were identified to enhance the inclusion of Cdh23 exon 68. The splicing of Cdh23 exon 68 is affected in Rbm24 knockdown or knockout cells. Moreover, we also found that PTBP1 inhibits the inclusion of Cdh23 exon 68. Taken together, we show here that alternative splicing of Cdh23 exon 68 is regulated by RBM24, RBM38, and PTBP1.http://dx.doi.org/10.1155/2020/8898811
spellingShingle Nana Li
Haibo Du
Rui Ren
Yanfei Wang
Zhigang Xu
Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
Neural Plasticity
title Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
title_full Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
title_fullStr Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
title_full_unstemmed Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
title_short Alternative Splicing of Cdh23 Exon 68 Is Regulated by RBM24, RBM38, and PTBP1
title_sort alternative splicing of cdh23 exon 68 is regulated by rbm24 rbm38 and ptbp1
url http://dx.doi.org/10.1155/2020/8898811
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AT ruiren alternativesplicingofcdh23exon68isregulatedbyrbm24rbm38andptbp1
AT yanfeiwang alternativesplicingofcdh23exon68isregulatedbyrbm24rbm38andptbp1
AT zhigangxu alternativesplicingofcdh23exon68isregulatedbyrbm24rbm38andptbp1