Predicting Functions of Uncharacterized Human Proteins: From Canonical to Proteoforms

Poverennaya, Ekaterina V.; Kiseleva, Olga I.; Pyatnitskiy, Mikhail A.

doi:10.3390/genes11060677

Cited by 11 publications

(6 citation statements)

References 69 publications

(95 reference statements)

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“…This intron position has been experimentally confirmed in Rhizophagus irregularis (accession GW123471). Since intron sliding is a known phenomenon [ 24 – 26 ] we cannot distinguish this apparent near coincidental intron position as the result of the sliding of a cognate intron from that of an independent near-coincident intronization event.…”

Section: Resultsmentioning

confidence: 99%

An ascomycete H4 variant with an unknown function

Flipphi,

Harispe,

Hamari

et al. 2024

R. Soc. Open Sci.

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Histone variants leading to altered nucleosome structure, dynamics and DNA accessibility occur frequently, albeit rarely for H4. We carried out a comprehensive in silico scrutiny of fungal genomes, which revealed the presence of a novel H4 variant (H4E) in the ascomycetes, throughout the Pezizomycotina, in basal species of the Taphrinomycotina and also in the Glomeromycota. The coding cognate genes show a specific intron/exon organization, different from H4 canonical genes. H4Es diverge from canonical H4s mainly in the N- and C-terminal extensions, showing marked differences in the distribution and number of Lys and Arg residues, which may result in novel post-translational modifications. In Aspergillus nidulans (Pezizomycotina, Eurotiomycetes) the H4E variant protein level is low in mycelia. However, the encoding gene is well expressed at 37°C under nitrogen starvation. H4E localizes to the nucleus and interacts with H3, but its absence or overexpression does not result in any detectable phenotype. Deletion of only one of the of the two canonical H4 genes results in a strikingly impaired growth phenotype, which indicates that H4E cannot replace this canonical histone. Thus, an H4 variant is present throughout a whole subphylum of the ascomycetes, but with hitherto no experimentally detectable function.

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Section: Resultsmentioning

confidence: 99%

An ascomycete H4 variant with an unknown function

Flipphi,

Harispe,

Hamari

et al. 2024

R. Soc. Open Sci.

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“…While aforementioned studies have primarily relied on gene expression analysis, an increasing volume of literature underscores the biomedical significance of protein isoforms, as these variants, originating from the same gene, can exhibit diverse biological functions and contribute differently to cellular processes [7][8][9][10], including oncogenesis [11,12]. In this study, we conducted a higherresolution analysis of the transcriptomic profiles of both normal and PML samples, with a specific focus on protein-coding transcripts rather than genes.…”

Section: Introductionmentioning

confidence: 99%

Transcript-Level Analysis of Molecular Alterations Associated With the Development of Premalignant Bronchial Lesions

Pyatnitskiy,

Poverennaya

2024

Preprint

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Premalignant lesions in the bronchial epithelium represent early stages of squamous cell lung carcinoma, challenging to detect with conventional methods. While previous studies have focused on gene expression, here we examine transcriptomic alterations associated with lesion development with the emphasis on protein-coding transcripts. We reanalyzed publicly available RNAseq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript abundances were quantified using kallisto, and differential expression and transcript usage analysis was conducted using the sleuth and RATs packages. Functional characterization included overrepresentation analysis (clusterProfiler), weighted co-expression network analysis (WGCNA), and network analysis (Enrichr-KG). We detected 5,906 differentially expressed transcripts, with significant enrichment in pathways related to oxidative phosphorylation and mitochondrial function. Transcript-level WGCNA identified single module correlated with dysplasia status, enriched in cilium-related biological processes. Analysis of hubs within this module highlighted key genes including RABL2B, DNAH1, EFHC1 and VWA3A, and revealed transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant lesion biology. By examining transcripts rather than genes, we identified potential biomarkers associated with early lung carcinogenesis.

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“…The accumulation of data on the proteome heterogeneity [ 12 , 13 ] and the functional differences between proteoforms [ 14 , 15 ] pushes the scientific community to rethink the distinction between the functions of a gene and a protein encoded by this gene.…”

Section: Introductionmentioning

confidence: 99%

Evolution of Protein Functional Annotation: Text Mining Study

Ilgisonis

Pogodin

Kiseleva

et al. 2022

JPM

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Within the Human Proteome Project initiative framework for creating functional annotations of uPE1 proteins, the neXt-CP50 Challenge was launched in 2018. In analogy with the missing-protein challenge, each command deciphers the functional features of the proteins in the chromosome-centric mode. However, the neXt-CP50 Challenge is more complicated than the missing-protein challenge: the approaches and methods for solving the problem are clear, but neither the concept of protein function nor specific experimental and/or bioinformatics protocols have been standardized to address it. We proposed using a retrospective analysis of the key HPP repository, the neXtProt database, to identify the most frequently used experimental and bioinformatic methods for analyzing protein functions, and the dynamics of accumulation of functional annotations. It has been shown that the dynamics of the increase in the number of proteins with known functions are greater than the progress made in the experimental confirmation of the existence of questionable proteins in the framework of the missing-protein challenge. At the same time, the functional annotation is based on the guilty-by-association postulate, according to which, based on large-scale experiments on API-MS and Y2H, proteins with unknown functions are most likely mapped through “handshakes” to biochemical processes.

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Predicting Functions of Uncharacterized Human Proteins: From Canonical to Proteoforms

Cited by 11 publications

References 69 publications

An ascomycete H4 variant with an unknown function

An ascomycete H4 variant with an unknown function

Transcript-Level Analysis of Molecular Alterations Associated With the Development of Premalignant Bronchial Lesions

Evolution of Protein Functional Annotation: Text Mining Study

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