Unveiling alterative splice diversity from human oligodendrocyte proteome data

Tavares, Raphael; Wajnberg, Gabriel; Scherer, Nicole de Miranda; Pauletti, Bianca Alves; Cassoli, Juliana S.; Ferreira, Carlos Gil; Leme, Adriana Franco Paes; Araujo-Souza, Patricia Savio de; Martins-de-Souza, Daniel; Passetti, Fábio

doi:10.1016/j.jprot.2016.05.023

Cited by 12 publications

(9 citation statements)

References 48 publications

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“…This indicates that the overexpression of PKM1 might be related to AD and that this peptide is a potential biomarker. Additionally, the proteoform PKM2 and isoform 3 ( HNRNPK gene) were inferred in MS/MS data from a large set of oligodendrocytes in a previous study [ 39 ], corroborating our findings. Interestingly, the switch over from PKM2 to PKM1 is known to be mediated by HNRNPK proteins [ 94 , 95 ].…”

Section: Discussionsupporting

confidence: 90%

“…Additionally, we removed AS variants that may be potential targets for the nonsense-mediated decay (NMD) pathway by identifying variants with a premature termination codon using the software NMD Classifier [37]. These sequences were then translated in silico and combined with UniProt/Swiss-Prot protein sequences (version 12_2020) [38] to build the custom protein sequence database, following the method described by Tavares et al (2017) [39]. Briefly, the sequences were divided into canonical and noncanonical proteoforms, and the noncanonical proteoforms were digested in silico by trypsin using a modified version of the Digest software (EMBOSS package version 6.3.1) [40].…”

Section: Protein Sequence Database Setupmentioning

confidence: 99%

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Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer’s Disease Mouse Model

Silva

Santos

Oliveira

et al. 2021

Cells

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Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer’s disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKCβII (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.

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Section: Discussionsupporting

confidence: 90%

Section: Protein Sequence Database Setupmentioning

confidence: 99%

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer’s Disease Mouse Model

Silva

Santos

Oliveira

et al. 2021

Cells

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“…al. identified 39 splice variants, including one variant from KRAS and the human glutaminase gene family respectively . Proteogenomics was also applied to unravel the spliceforms and unannotated proteins in Arabidopsis seedlings in response to abscisic acid (ABA) treatment, whereby it was discovered that ABA causes increased number of non‐conventional splicing sites, especially alternative first exons (AFE) and alternative last exons (ALE) …”

Section: Applications Of Proteogenomics In Biologymentioning

confidence: 99%

Connecting Proteomics to Next‐Generation Sequencing: Proteogenomics and Its Current Applications in Biology

et al. 2018

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Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains is limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines. In this review, how genomics and transcriptomics data in different formats can be utilized to assist proteogenomics application is briefly discussed. Subsequently, a much larger part of this review focuses on proteogenomics research articles that are published in the last five years that answer two important questions. First, how proteogenomics can be applied to tackle biological problems is discussed, covering genome annotation and precision medicine. Second, the latest developments in analytical technologies for data acquisition and the bioinformatics tools to interpret and visualize proteogenomics data are covered.

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“…These nascent premature transcripts then undergo splicing, where introns are removed from the mRNA sequence and exons are stitched together . The variety of isoforms that can be generated through splicing from a single gene can augment the diversity of functions of the resulting proteins . After splicing, the mature mRNA is exported from the nucleus, translated in the cytoplasm by ribosomes, and the resulting peptides are folded and assembled into functional units .…”

Section: Dna–rna Interactionsmentioning

confidence: 99%

“…39 The variety of isoforms that can be generated through splicing from a single gene can augment the diversity of functions of the resulting proteins. 39,40 After splicing, the mature mRNA is exported from the nucleus, translated in the cytoplasm by ribosomes, and the resulting peptides are folded and assembled into functional units. 41 Understanding the details underlying this process is critical to paint a complete picture of how disruptions or mistakes during transcription can lead to disease states.…”

Section: Dna-rna Interactionsmentioning

confidence: 99%

Insights into nuclear dynamics using live‐cell imaging approaches

Bigley

Payumo

Alexander

et al. 2017

WIREs Mechanisms of Disease

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The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide “omic” approaches have become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems. Live-cell imaging approaches are capable of providing quantitative assessment of the dynamics of gene regulatory interactions within the nucleus. We survey recent insights into what live-cell imaging approaches have provided the field of nuclear dynamics. In this review, we focus on interactions of DNA with other DNA loci, proteins, RNA, and the nuclear envelope.

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Unveiling alterative splice diversity from human oligodendrocyte proteome data

Cited by 12 publications

References 48 publications

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer’s Disease Mouse Model

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer’s Disease Mouse Model

Connecting Proteomics to Next‐Generation Sequencing: Proteogenomics and Its Current Applications in Biology

Insights into nuclear dynamics using live‐cell imaging approaches

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