Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

Shi, De-Li; Cheng, Xiao-Ning; Saquet, Audrey; Grifone, Raphaëlle

doi:10.3390/ijms232012393

Cited by 8 publications

(5 citation statements)

References 85 publications

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“…Similarly to photoreceptors and other neurons, SRRM4 targets in hair cells comprise stereocilia genes as well as secretory and synaptic genes. Since then, other SFs have been identified as relevant for hearing and hair cell development and function (Shi et al, 2022 ). Sfswap is widely expressed in mice developing inner ear and mature cochlea (Moayedi et al, 2014 ).…”

Section: As and Srs In Other Ciliated Sensory Cells: Hair Cells And O...mentioning

confidence: 99%

Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States

Ciampi,

Serrano,

Irimia

2024

Mol Syst Biol

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Alternative Splicing (AS) programs serve as instructive signals of cell type specificity, particularly within the brain, which comprises dozens of molecularly and functionally distinct cell types. Among them, retinal photoreceptors stand out due to their unique transcriptome, making them a particularly well-suited system for studying how AS shapes cell type-specific molecular functions. Here, we use the Splicing Regulatory State (SRS) as a novel framework to discuss the splicing factors governing the unique AS pattern of photoreceptors, and how this pattern may aid in the specification of their highly specialized sensory cilia. In addition, we discuss how other sensory cells with ciliated structures, for which data is much scarcer, also rely on specific SRSs to implement a proteome specialized in the detection of sensory stimuli. By reviewing the general rules of cell type- and tissue-specific AS programs, firstly in the brain and subsequently in specialized sensory neurons, we propose a novel paradigm on how SRSs are established and how they can diversify. Finally, we illustrate how SRSs shape the outcome of mutations in splicing factors to produce cell type-specific phenotypes that can lead to various human diseases.

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Section: As and Srs In Other Ciliated Sensory Cells: Hair Cells And O...mentioning

confidence: 99%

Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States

Ciampi,

Serrano,

Irimia

2024

Mol Syst Biol

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“…Also confounding any conclusion are the many roles RBPs play in mRNA regulation, which include coordination of translation, monitoring of mRNA stability and decay, and mRNA transport between organelles (Gerstberger et al, 2014). Indeed, there is ample evidence that RBPs regulate cochlear development via mechanisms unrelated to AS (Shi et al, 2022). Therefore, the effect of an RBP on cell function or survival cannot be attributed to AS alone without sufficient evidence.…”

Section: Regulation Of Alternative Splicing In the Cochleamentioning

confidence: 99%

“…Alternative promoters, alternative translation start/stop sites, and post-translational modifications are all examples of post-transcriptional regulatory mechanisms that can contribute to isoform diversity (Hu et al, 2015;Reyes and Huber, 2018). Recent studies have explored the result of these processes in the cochlea, and comprehensive reviews have been written on this subject (Booth et al, 2018a;Shi et al, 2022). In this article, we focus on alternative splicing (AS), a post-transcriptional modification process that allows the production of multiple mRNA transcripts from a single gene.…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing in shaping the molecular landscape of the cochlea

Kim

Koo²,

Bok³

2023

Front. Cell Dev. Biol.

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The cochlea is a complex organ comprising diverse cell types with highly specialized morphology and function. Until now, the molecular underpinnings of its specializations have mostly been studied from a transcriptional perspective, but accumulating evidence points to post-transcriptional regulation as a major source of molecular diversity. Alternative splicing is one of the most prevalent and well-characterized post-transcriptional regulatory mechanisms. Many molecules important for hearing, such as cadherin 23 or harmonin, undergo alternative splicing to produce functionally distinct isoforms. Some isoforms are expressed specifically in the cochlea, while some show differential expression across the various cochlear cell types and anatomical regions. Clinical phenotypes that arise from mutations affecting specific splice variants testify to the functional relevance of these isoforms. All these clues point to an essential role for alternative splicing in shaping the unique molecular landscape of the cochlea. Although the regulatory mechanisms controlling alternative splicing in the cochlea are poorly characterized, there are animal models with defective splicing regulators that demonstrate the importance of RNA-binding proteins in maintaining cochlear function and cell survival. Recent technological breakthroughs offer exciting prospects for overcoming some of the long-standing hurdles that have complicated the analysis of alternative splicing in the cochlea. Efforts toward this end will help clarify how the remarkable diversity of the cochlear transcriptome is both established and maintained.

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“…RNA-binding proteins (RBPs) play important roles in maintaining physiological homeostasis and are key players in posttranscriptional events ( 2 ). RBPs are involved in the development and progression of various diseases, including cardiovascular disease, genetic disease, and neurodegenerative disorders ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a prognostic model based on RNA binding proteins in patients with esophageal cancer

Du,

Li,

Pang

et al. 2023

J Thorac Dis

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Background RNA-binding proteins (RBPs) play a crucial role in regulating RNA turnover and are associated with cancer development. However, little is known about the role of RBPs in esophageal cancer (ESCA). The present study focuses on the association between RBP gene expression and survival in ESCA, addressing the clinical relevance of an RBPs-based prediction model for prognosis. Methods RNA-sequencing data and clinical information of patients with ESCA were obtained from The Cancer Genome Atlas (TCGA) database. We identified differentially expressed genes in ESCA and intersected them with RBP-encoding genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with the identified differentially expressed RBPs. Then, a protein-protein interaction (PPI) network was constructed through the STRING database to determine the hub RBPs. Univariate Cox regression analysis and multivariate Cox regression analysis were applied to construct a novel prognostic model based on RBPs. Based on the R package “Caret”, we divided patients into the training set and validation set. The efficacy of the prognostic model was evaluated by the area under the receiver operating characteristic (ROC) curve. A nomogram was developed for the prediction of patient survival outcomes. Results A total of 158 ESCA patients from the TCGA database were included in our analysis. We screened out five prognostic RBPs (CLK1, CIRBP, MRPL13, TNRC6A, and TYW3) through univariate and multivariate Cox regression analysis. CLK1, CIRBP, TNRC6A and TYW3 were downregulated in tumor samples, while MRPL13 was upregulated. A prognostic model constructed with these five RBPs in the training data set accurately stratified ESCA patients into high- and low-risk groups. When the same prognostic model was applied to the test data set and entire cohort, the 5-RBP signature remained an independent prognostic factor in multivariate analysis. The areas under the time-dependent ROC curve of the prognostic model for predicting one-year survival in the training data set, test data set, and entire cohort were 0.789, 0.753, and 0.764, respectively, confirming that this model is a good prognostic model. The nomogram based on the five RBPs and clinical variables could improve individualized outcome predictions and highlight the importance of RBPs in the outcomes of patients with ESCA. Conclusions Our study provides a potential prognostic model for predicting the prognosis of ESCA patients. The prognostic nomogram could improve individualized outcome predictions for patients with ESCA, therefore providing novel insights into future diagnosis and treatment.

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Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

Cited by 8 publications

References 85 publications

Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States

Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States

Alternative splicing in shaping the molecular landscape of the cochlea

Development and validation of a prognostic model based on RNA binding proteins in patients with esophageal cancer

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