Predictive models of subcellular localization of long RNAs

Zuckerman, Bert M.; Ulitsky, Igor

doi:10.1261/rna.068288.118

Cited by 83 publications

(92 citation statements)

References 76 publications

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“…An analysis of lncRNA in TEX-treated human tumor cells provided similar results with a dominance of chromosome modulation, followed by miRNA sponging, engagement in protein complex formation frequently including RBP and being involved in splicing and translation, and least frequently in transcription initiation. Finally, the vast majority of these lncRNAs are engaged in several functions, which is well in line with lncRNA shuttling between the nucleus, mitochondria, and cytoplasm [82,[122][123][124][125][126].…”

Section: Lncrna Shuttling: Melding and Resolving The Distinct Ev Actimentioning

confidence: 76%

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

Provazník

Hackert

et al. 2020

Cells

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Tumor cell-derived extracellular vesicles (TEX) expressing tetraspanin Tspan8-alpha4/beta1 support angiogenesis. Tspan8-alpha6/beta4 facilitates lung premetastatic niche establishment. TEX-promoted target reprogramming is still being disputed, we explored rat endothelial cell (EC) and lung fibroblast (Fb) mRNA and miRNA profile changes after coculture with TEX. TEX were derived from non-metastatic BSp73AS (AS) or metastatic BSp73ASML (ASML) rat tumor lines transfected with Tspan8 (AS-Tspan8) or Tspan8-shRNA (ASML-Tspan8kd). mRNA was analyzed by deep sequencing and miRNA by array analysis of EC and Fb before and after coculture with TEX. EC and Fb responded more vigorously to AS-Tspan8- than AS-TEX. Though EC and Fb responses differed, both cell lines predominantly responded to membrane receptor activation with upregulation and activation of signaling molecules and transcription factors. Minor TEX-initiated changes in the miRNA profile relied, at least partly, on long noncoding RNA (lncRNA) that also affected chromosome organization and mRNA processing. These analyses uncovered three important points. TEX activate target cell autonomous programs. Responses are initiated by TEX targeting units and are target cell-specific. The strong TEX-promoted lncRNA impact reflects lncRNA shuttling and location-dependent distinct activities. These informations urge for an in depth exploration on the mode of TEX-initiated target cell-specific remodeling including, as a major factor, lncRNA.

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Section: Lncrna Shuttling: Melding and Resolving The Distinct Ev Actimentioning

confidence: 76%

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

Provazník

Hackert

et al. 2020

Cells

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“…We argue that cells can regulate the subcellular localization and biological functions of RNAs through alternative splicing of introns, which contain localization elements (RNA structure context or sequence motifs). These findings can help us better understand the regulatory mechanisms of RNA localization, and thus, for example, predict RNA localization more precisely from sequence characteristics [76].…”

Section: Discussionmentioning

confidence: 87%

RNA-Seq Analysis Reveals Localization-Associated Alternative Splicing across 13 Cell Lines

Zeng

Hamada

2020

Genes

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Alternative splicing, a ubiquitous phenomenon in eukaryotes, is a regulatory mechanism for the biological diversity of individual genes. Most studies have focused on the effects of alternative splicing for protein synthesis. However, the transcriptome-wide influence of alternative splicing on RNA subcellular localization has rarely been studied. By analyzing RNA-seq data obtained from subcellular fractions across 13 human cell lines, we identified 8720 switching genes between the cytoplasm and the nucleus. Consistent with previous reports, intron retention was observed to be enriched in the nuclear transcript variants. Interestingly, we found that short and structurally stable introns were positively correlated with nuclear localization. Motif analysis reveals that fourteen RNA-binding protein (RBPs) are prone to be preferentially bound with such introns. To our knowledge, this is the first transcriptome-wide study to analyze and evaluate the effect of alternative splicing on RNA subcellular localization. Our findings reveal that alternative splicing plays a promising role in regulating RNA subcellular localization.

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“…According to Zhang et al's article [37], mutational analyses showed that a novel RNA pentamer sequence motif, AGCCC, mediated the nucleus localization of lncRNA BORG with a sequence limitation at positions -8 (T or A) and -3 (G or C) relative to the first nucleotide of the pentamer. On the report of Zuckerman and Ulitsky [38], the preference for C-rich hexamers correlated with nucleus enrichment. Moreover, the biological mechanism of CG-contented octamer trimodal spectrum was unique [39].…”

Section: B Feature Representation 1) K-mer Nucleotide Composition Fementioning

confidence: 90%

lncLocPred: Predicting LncRNA Subcellular Localization Using Multiple Sequence Feature Information

2020

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Determining the subcellular localization of long non-coding RNAs (lncRNAs) provides very favorable references to discover the function of lncRNAs. Instead of through time-consuming and expensive biochemical experiments, we develop a machine learning predictor based on logistic regression, lncLocPred, to predict the subcellular localization of lncRNAs. We adopt sequence features including k-mer, triplet, and PseDNC and systematically process feature selection through VarianceThreshold, binomial distribution, and F-score to obtain representative features. We observe that the top-ranked k-mers have a higher base content of G and C in the form of short repeats. Improving prediction accuracy on several subcellular localizations, our model achieves the highest overall accuracy of 92.37% on the benchmark dataset by jackknife, higher than the existing state-of-the-art predictors. Additionally, lncLocPred performs better for the prediction on an independent dataset collected by us as well. Related experimental data and source code are available at https://github.com/jademyC1221/lncLocPred.

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Predictive models of subcellular localization of long RNAs

Cited by 83 publications

References 76 publications

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response

RNA-Seq Analysis Reveals Localization-Associated Alternative Splicing across 13 Cell Lines

lncLocPred: Predicting LncRNA Subcellular Localization Using Multiple Sequence Feature Information

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