Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences

Regulapati, Rahul; Bhasi, Ashwini; Singh, Chandan Kumar; Senapathy, Periannan

doi:10.1371/journal.pone.0003456

Cited by 8 publications

(22 citation statements)

References 41 publications

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“…Considering that the longer the transcript is, the higher the splicing frequency (or exon number) should be [45], we next determined the association between the length of the transcript and its subcellular localization. We evaluated the relationship between length and subcellular localization by calculating the length ratio (logarithmic scale) between the cytoplasmic transcript and the nuclear transcript in each transcript switch.…”

Section: A Transcript Switch Is Associated With Rna Splicing Rather Tmentioning

confidence: 99%

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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Section: A Transcript Switch Is Associated With Rna Splicing Rather Tmentioning

confidence: 99%

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

Zeng

Hamada

2020

Genes

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“…Figure S3A, right panels). In the human genome, gene length is proportional to the number of introns that a gene contains (16). Therefore, our next question was whether the number of introns correlated to the change in expression caused by prefoldin knockdowns.…”

Section: Prefoldin Deficiency Causes Stronger Expression Defects In Lmentioning

confidence: 99%

Human prefoldin modulates co-transcriptional pre-mRNA splicing

Payán-Bravo

Peñate

Cases

et al. 2020

Preprint

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Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the cotranslational folding of actin and tubulin monomers. Additional functions of prefoldin in the cell nucleus have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin depletion provoked transcriptional alterations across the genome of human cells. Severe pre-mRNA splicing defects were also detected, particularly under serum stimulation conditions. We found a significant impairment of co-transcriptional splicing during transcription elongation, that explains why the expression of long genes with a high number of introns was affected the most. We detected prefoldin binding to the gene body of transcribed genes and found that its lack caused significant decrease in the levels of Ser2 phosphorylation of the RNA polymerase II carboxiterminal domain. Moreover, lack of prefoldin reduced the association of splicing factor U2AF65 with chromatin, an association that is known to be dependent on Ser2 phosphorylation. Considered altogether the reported results indicate that human prefoldin is able to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing efficiency.

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“…Considering that the longer the transcript is, the higher the splicing frequency (or exon number) should be 45 , we next Mood's median test). (C) Comparison of ∆TU between mono-exonic (black) and multi-exonic (red) transcripts across 13 cell lines.…”

Section: A Transcript Switch Is Associated With Rna Splicing Rather Tmentioning

confidence: 99%

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

Zeng

Hamada

2019

Preprint

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Background: Alternative splicing, a ubiquitous phenomenon in eukaryotes, provides a regulatory mechanism for the biological diversity of individual genes.Most studies have focused on the e↵ects of alternative splicing for protein synthesis. However, the influence of alternative splicing on the RNA subcellular localization has rarely been studied.Results: By analyzing RNA-seq data from subcellular fractions across thirteen human cell lines, we observed that splicing is apparent to promote cytoplasmic localization. We also discovered that intron retention is preferred by transcripts localized in the nucleus. Short and structurally stable introns show a positive correlation with nuclear localization. Such introns are predicted to be preferentially bound by MBNL1, an RNA-binding protein that contains two nuclear localization signals.Conclusions: Our findings reveal that alternative splicing plays an important role in regulating RNA subcellular localization. This study provides valuable clues for understanding the biological mechanisms of alternative splicing. 1 2 3Most eukaryotic genes consist of exons (encoding mature RNAs) and introns (re-4 moved by RNA splicing). Alternative splicing is known as a regulated process by 5 which exons can be either included or excluded. Various RNAs (also called transcript 6 variants) can be produced from a single gene through alternative splicing. Thus, al-7 ternative splicing enables a cell to express more RNA species with a limited number 8 of genes, which increases the genome complexity [1]. In humans, for instance, about 95% of the multi-exonic genes undergoing alternative splicing were uncovered by 1 high-throughput sequencing technology [2]. Exploring the functionality of alterna-2 tive splicing is critical to our understanding of life mechanisms. Alternative splicing 3 has been reported to be associated with protein functions, such as diversification, 4 molecular binding properties, catalytic and signaling abilities, and stability. Such 5 related studies have been reviewed elsewhere [3, 4]. Additionally, relationships be-6 tween alternative splicing and disease [5] or cancer [6, 7] has received increasing 7 attention. Understanding the pathogenesis associated with alternative splicing can 8 shed light on diagnosis and therapy. With the emergence and rapid development 9 of high-throughput technology, it has become possible to study the function and 10 mechanism of alternative splicing genome-wide [8]. 11The location of an RNA in a cell can determine whether the RNA is translated, 12 preserved, modified, or degraded [9, 10]. In other words, the subcellular location of 13 an RNA is highly related to its biological function [9]. For example, the asymmetric 14 distribution of RNA in cells can influence the expression of genes [9], the forma-15 tion and interaction of protein complexes [11], the biosynthesis of ribosomes [12],the 16 development of cells [13, 14], among other functions. Many techniques have been de-17 veloped to investigate the subcellular localization of RNAs. RN...

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Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences

Cited by 8 publications

References 41 publications

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

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

Human prefoldin modulates co-transcriptional pre-mRNA splicing

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

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