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Towards resolution of the intron retention paradox in breast cancer

ABSTRACT: Towards resolution of the intron retention paradox in breast cancer

PROVIDER: PRJNA805511 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17982654_1.fastq.gz	Fastqsanger.gz
	SRR17982654_2.fastq.gz	Fastqsanger.gz
	SRR17982655_1.fastq.gz	Fastqsanger.gz
	SRR17982655_2.fastq.gz	Fastqsanger.gz
	SRR17982656_1.fastq.gz	Fastqsanger.gz

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Towards resolution of the intron retention paradox in breast cancer

Project description:We explored intron retention patterns in normal breast epithelial cells (MCF10A) and estrogen receptor positive (ER+) breast cancer cells (MCF7).

2022-12-31 | GSE196557 | GEO

Towards resolution of the intron retention paradox in breast cancer.

Project description:BackgroundAfter many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue.MethodsIn this study, we have conducted a pan-cancer analysis of IR with emphasis on BrCa and its subtypes. We explored mechanisms that could cause aberrant and pathological IR and clarified why normal breast tissue has unusually high IR.ResultsStrikingly, we found that aberrantly decreasing IR in BrCa can be largely attributed to normal breast tissue having the highest occurrence of IR events compared to other healthy tissues. Our analyses suggest that low numbers of IR events in breast tumours are associated with poor prognosis, particularly in the luminal B subtype. Interestingly, we found that IR frequencies negatively correlate with cell proliferation in BrCa cells, i.e. rapidly dividing tumour cells have the lowest number of IR events. Aberrant RNA-binding protein expression and changes in tissue composition are among the causes of aberrantly decreasing IR in BrCa.ConclusionsOur results suggest that IR should be considered for therapeutic manipulation in BrCa patients with aberrantly low IR levels and that further work is needed to understand the cause and impact of high IR in other tumour types.

| S-EPMC9798573 | biostudies-literature

Intron retention analysis using isogrowth profiling

Project description:Intron retention analysis using isogrowth profiling

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Intron retention analysis using isogrowth profiling

Project description:We present an analysis of intron retention under stress from two different drugs and their combinations in yeast Saccharomyces cerevisiae. We previously established isogrowth profiling, a method to abstract the non-specific effects of growth rate inhibition from the specific effect of perturbation by a small molecule: two drugs are used at varied ratios, but at fixed overall growth inhibition. Here, cycloheximide and LiCl were used at seven different ratios along the 50% growth inhibition isobole and the total ribodepleted RNA was sequenced. This allowed us to gauge the changes in intron retention due to the used drugs, while ensuring that the effects are not caused by growth inhibition. We found a prominent increase in intron retention under LiCl treatment that preferentially affects introns contained in the transcripts of ribosomal proteins.

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Dynamic intron retention modulates gene expression in the monocytic differentiation pathway

Project description:We determined the role of intron retention in murine monocyte differentiation

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Stress-induced transcriptional readthrough into neighboring genes is linked to intron retention

Project description:Exposure to certain stresses leads to readthrough transcription downstream of gene ends. Here we found that this phenomenon impacts the expression of genes located downstream to readthrough genes, whereby readthrough transcription proceeds into downstream genes, termed read-in genes. Using polyA-selected RNA-seq data from mouse fibroblasts, we identified widespread read-in in heat shock, oxidative and osmotic stress conditions. Read-in genes share distinctive genomic characteristics; they are extremely short, mainly due to less, shorter, introns, and they are highly GC rich. Furthermore, using ribosome footprint profiling we found that the translation of genes with high degrees of read-in is significantly reduced. Strikingly, read-in genes show extremely high levels of intron retention during stress, mostly in their first intron. While read-in genes share features that are generally associated with increased likelihood of intron retention, such as short introns and high GC content, intron retention in read-in genes during stress exceeds greatly beyond what is expected given their genomic properties. Finally, we found that first introns in read-in genes have weaker 5’ and 3’ splice sites. Our data portray a relationship between read-in and intron retention, suggesting it may have co-evolved to facilitate reduced translation of read-in genes during stress.

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Gene expression and intron retention analysis of ZCRB1-knockdown human cells

Project description:ZCRB1 is a RNA binding protein involved in the Minor Spliceosome. Here, we used shRNAs to knock down ZCRB1 in HCT116 cells to analysis the function of ZCRB1 in gene expression and intron retention.

2023-04-10 | GSE182830 | GEO

Gene expression and intron retention analysis of 15.5K-knockdown human cells

Project description:15.5K is a RNA binding protein involved in the Minor Spliceosome. Here, we used shRNAs to knock down 15.5K in HEK293T cells to analysis the function of 15.5K in gene expression and intron retention.

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