Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [CHyMErA]

ABSTRACT: Thousands of human introns harbour extended regions of high evolutionarily conservation that have not been previously characterized. A survey of these sequences reveals that they are associated with intron retention and enriched in genes that function in RNA processing, chromatin remodelling and neuronal biology. Using a dual CRISPR-Cas editing approach, we targeted 2,600 of these regions for deletion and observe that a subset of these perturbations affectaffects cell growth. Many of these ‘fitness’ sequences affect intron retention and or expression levels of their host genes. Deletions in nuclear speckle-associated retained introns in the FNBP4 and DDX5 genes are further linked to downstream effects on cell growth-related genes and intron retention, respectively. The DDX5 deletion additionally results in the accumulation of R-loops overlapping first introns in speckle-proximal genes. Overall, the results highlight multifactetedmultifaceted, critical roles of highly conserved intronic sequences in the control of gene regulation, R-loop resolution and cell growth.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE296292 | GEO | 2026/06/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_CHX]

Project description:Thousands of human introns harbour extended regions of high evolutionarily conservation that have not been previously characterized. A survey of these sequences reveals that they are associated with intron retention and enriched in genes that function in RNA processing, chromatin remodelling and neuronal biology. Using a dual CRISPR-Cas editing approach, we targeted 2,600 of these regions for deletion and observe that a subset of these perturbations affectaffects cell growth. Many of these ‘fitness’ sequences affect intron retention and or expression levels of their host genes. Deletions in nuclear speckle-associated retained introns in the FNBP4 and DDX5 genes are further linked to downstream effects on cell growth-related genes and intron retention, respectively. The DDX5 deletion additionally results in the accumulation of R-loops overlapping first introns in speckle-proximal genes. Overall, the results highlight multifactetedmultifaceted, critical roles of highly conserved intronic sequences in the control of gene regulation, R-loop resolution and cell growth.

2026-06-18 | GSE296298 | GEO

A genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_candidates.RPE1]

2026-06-18 | GSE296306 | GEO

A genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [RNAseq_candidates.HAP1]

2026-06-18 | GSE296299 | GEO

The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis

Project description:RNA localization adds a fundamental layer to gene expression by determining when and where translation-ready mRNAs become available. Here, we identify a distinct subnuclear RNA niche at the nuclear speckle periphery that links intron retention to cell-cycle-timed RNA release. Using compartment-resolved transcriptional inhibition, sequence-based deep learning, and single-molecule and super-resolution RNA imaging in human pluripotent stem cells, we define a class of nuclear RNAs with long-lived retained introns (LL-IR-RNAs) that maintain stable intron retention for hours and are enriched in genome maintenance and mitosis regulators, including centromere and kinetochore assembly, DNA repair, and telomere maintenance. Long-lived retained introns are characterized by elevated GC content, predicted structural stability, and nuclear speckle-associated RBPs. In interphase, LL-IR-RNAs localize to a nuclear speckle-proximal niche conserved between cell types. During mitotic remodeling, they undergo coordinated, kinase-dependent splicing and populate the cytoplasm of early G1 daughter cells. These findings link cis-encoded intronic features, subnuclear organization and mitotic remodeling to temporal control of RNA fate.

2026-06-24 | GSE327794 | GEO

Spontaneous mutations in FgSAD1 suppress the growth defect of the Fgprp4 mutant by affecting tri-snRNP stability and its docking in Fusarium graminearum

Project description:Purpose: For detecting splicing defects in wild type PH-1 and sector S139 and transformant D10. Our results showed that S139 and D10 had similar intron retention levels (un-spliced introns). The intron retention levels in S139 were significantly higher than those in PH-1 (P<0.001,t-test). For the 15,211 introns in the 6,995 genes expressed across two strains, approximately 25% of them had an over 2-fold intron retention rate in comparison with the intron retention rate in PH-1, indicating splicing defects in S139 and D10.

2019-05-15 | GSE131206 | GEO

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.

2022-10-27 | GSE197536 | GEO

Detained introns are novel, widespread class of posttranscriptionally-spliced introns

2015-01-15 | GSE57231 | GEO

Detained introns are novel, widespread class of posttranscriptionally-spliced introns

Project description:Removal of introns by pre-mRNA splicing is a critical and in some cases rate-limiting step in mammalian gene expression. Deep sequencing of mouse embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within poly(A) selected transcripts; we classify these as “detained” introns (DIs). We identified thousands of DIs flanking both constitutive and alternatively spliced exons in human and mouse cell lines. Drug inhibition of Clk SR-protein kinase activity triggered rapid splicing changes in a specific set of DIs, about half of which showed increased splicing and half increased intron detention, altering the transcript pool of over 300 genes. These data suggest a widespread mechanism by which a nuclear detained pool of mostly processed pre-mRNAs can be rapidly mobilized in response to stress or homeostatic autoregulation. v6.5 mouse embryonic stem cells were untreated, treated with the Clk kinase inhibitor KH-CB19, or treated with DMSO as a negative control. Untreated cells were harvested and a single replicate was sequenced using a custom, ligation-based, stranded library preparation protocol. Treated cells were harvested at time 0 and at 2 hours post-treatment, and poly(A)-selected RNA-seq libraries were made from biological duplicates for each treatment/time, barcoded, and sequenced by strand-specific, paired-end sequencing using the Illumina TruSeq kit.

2015-01-15 | E-GEOD-57231 | biostudies-arrayexpress

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.

2022-02-15 | GSE155060 | GEO

Chromosomal instability by mutations in the novel minor spliceosome component CENATAC

Project description:Aneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations in CENATAC (CCDC84). We show that CENATAC is a novel component of the minor (U12-dependent) spliceosome that promotes splicing of a specific, rare minor intron subtype. This subtype is characterized by AT-AN splice sites and relatively high basal levels of intron retention. CENATAC depletion or expression of disease mutants resulted in excessive retention of AT-AN minor introns in ~100 genes enriched for nucleocytoplasmic transport and cell cycle regulators, and caused chromosome segregation errors. Our findings reveal selectivity in minor intron splicing and suggest a link between minor spliceosome defects and constitutional aneuploidy in humans.

2021-04-07 | PXD024682 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data