Neuron-specific splicing

Hakim, Nor Hakimah Ab; Majlis, Burhanuddin Yeop; Suzuki, Hitoshi; Tsukahara, Toshifumi

doi:10.5582/bst.2016.01169

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…However, identifying a reliable set of marker genes can be challenging, especially for neuronal tissues with complex cell type taxonomy (Kiselev et al, 2017). Since AS is known to be more prevalent in the brain (Dai et al, 2010;Hakim et al, 2017), we hypothesized that splicing events are more reliable for distinguishing cell types than gene expression. We refer to splicing nodes that are highly included or excluded in only one cell type as marker nodes in analogy with marker genes.…”

Section: Splicing Events Are More Precise Markers Of Cell Typesmentioning

confidence: 99%

Mining alternative splicing patterns in scRNA-seq data using scASfind

Song,

Parada,

Lee

et al. 2023

Preprint

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Single-cell RNA-seq is widely used for transcriptome profiling, but most analyses have focused on gene-level events, with much less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events. scASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and large blocks of exons that are specific to one or more cell types. These methods allow researchers to compare cells based on isoforms rather than genes, thereby enabling more nuanced characterization of cell types and states. We demonstrate the advantages of scASfind on two mouse and one human datasets, identifying differences across the several key genes that cannot be detected using gene expression alone.

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Section: Splicing Events Are More Precise Markers Of Cell Typesmentioning

confidence: 99%

Mining alternative splicing patterns in scRNA-seq data using scASfind

Song,

Parada,

Lee

et al. 2023

Preprint

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“…RNA-binding proteins (RBPs) bind to pre-mRNAs and mRNAs and thereby tightly control AS or mRNA translation and stability, in a cell-type-specific manner, especially in neurons 22,23 . To identify the explicit RPBs enriched for each AS events and evaluate their possible biological effect in differentiated SH-SY5Y cells, motif enrichment analysis using rMAPS2 was performed with differential AS data generated from rMATS.…”

Section: Analysis Of Local Splicing Events (Lsvs) and Rna-binding Proteins (Rbps) Motif Enrichmentmentioning

confidence: 99%

Mature Neurons’ sensitivity to oxidative stress is epigenetically programmed by alternative splicing and mRNA stability

Yuan

Rashad

Tominaga

et al. 2021

Preprint

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Neuronal differentiation is a complex process that entails extensive morphological, transcriptional, metabolic, and functional changes that dictate neuronal lineage commitment. Much less understood is the role that epigenetic and epi-transcriptional reprogramming plays in the process of neuronal differentiation and maturation. To depict the whole landscape of transcriptomics and epigenetic changes during neuronal differentiation and maturation, we differentiated SH-SY5Y cells and performed RNA sequencing on differentiated and undifferentiated cells. 728 differentially expressed genes (DEGs) enriched in synaptic signaling and cell morphogenesis pathways were observed. Moreover, transcriptome-wide mRNA stability profiling revealed that genes with altered stability were exceptionally enriched for redox homeostasis pathways. Mature neurons are known to be highly sensitive to oxidative stress, which is crucial in the pathophysiology of neurodegenerative disease. Our results suggest that this heightened sensitivity is regulated at the mRNA stability level (i.e., epigenetic) rather than at the transcriptional level. Alternative splicing analysis revealed the exon skipping and alternative mRNA isoforms enriched for morphogenesis related pathway. Alternatively, alternative 5 and 3 prime splicing site, intron retention and mutually exclusive exon events exclusively clustered in the translation and translation initiation pathways, suggesting the potential effect of alternative splicing on translation following neuronal maturation. Splice motif analysis revealed enriched motifs for RBPs that regulate various splice types and can be further correlated to distinct phenotypical changes during neuronal differentiation and maturation. Here we present an extensive exploration of the transcriptional and epigenetic changes and their potential association with the process of neuronal differentiation, providing a new insight into understanding the molecular mechanism of neuronal function and behavior.

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“…While some RBPs are ubiquitously expressed and involved in essential cell functions, many are cell typespecific and thereby fine tune functions that contribute to physiologic roles unique to those cells, such as neurons (Conboy, 2017;Gerstberger et al, 2014;Hakim et al, 2017;Nikonova et al, 2019;Van Nostrand et al, 2020a). We identified ESRP1 and ESRP2 as paralogous epithelial cell type-specific specific splicing regulatory proteins (Warzecha et al, 2009a;Warzecha et al, 2009b).…”

Section: Introductionmentioning

confidence: 98%

The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function

Hwang

Quesnel-Vallières

et al. 2021

Preprint

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The epithelial splicing regulatory proteins, ESRP1 and ESRP2 are essential for mammalian development through regulation of a global program of alternative splicing of genes involved in maintenance of epithelial cell function. To further inform our understanding of the molecular functions of ESRP1 we performed enhanced crosslinking immunoprecipitation coupled with high throughput sequencing (eCLIP) in epithelial cells of mouse epidermis. The genome-wide binding sites of ESRP1 were integrated with RNA-Seq analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2. These studies demonstrated that ESRP1 functions in splicing regulation occur primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In addition, we also identified widespread binding of ESRP1 in 3′ and 5′ untranslated regions (UTRs) of genes involved in epithelial cell function suggesting that its post-transcriptional functions extend beyond splicing regulation.

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Neuron-specific splicing

Cited by 13 publications

References 36 publications

Mining alternative splicing patterns in scRNA-seq data using scASfind

Mining alternative splicing patterns in scRNA-seq data using scASfind

Mature Neurons’ sensitivity to oxidative stress is epigenetically programmed by alternative splicing and mRNA stability

The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function

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