Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Essential lncRNAs in the human transcriptome [CRISPR]

ABSTRACT: Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using RNA-targeting CRISPR-Cas13 screens, we probed how loss of ~5,500 lncRNAs impacts cell fitness across five human cell lines and identified 788 lncRNAs with context-specific or broad essentiality. We confirm their essentiality with individual perturbations and find that the majority of essential lncRNAs operate independently of their nearest protein-coding genes. Using transcriptome profiling in single cells, we discover that loss of essential lncRNAs impair cell cycle progression and drive apoptosis. Many essential lncRNAs demonstrate dynamic expression across tissues during development. Using ~9,000 primary tumors, we pinpoint those lncRNAs whose expression in tumors correlates with survival, yielding new biomarkers and potential therapeutic targets. This transcriptome-wide survey of functional lncRNAs advances our understanding of noncoding transcripts and demonstrates the potential of transcriptome-scale noncoding screens with Cas13.

ORGANISM(S): Homo sapiens

PROVIDER: GSE326978 | GEO | 2026/04/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Essential lncRNAs in the human transcriptome

Project description:Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using RNA-targeting CRISPR-Cas13 screens, we probed how loss of ~5,500 lncRNAs impacts cell fitness across five human cell lines and identified 788 lncRNAs with context-specific or broad essentiality. We confirm their essentiality with individual perturbations and find that the majority of essential lncRNAs operate independently of their nearest protein-coding genes. Using transcriptome profiling in single cells, we discover that loss of essential lncRNAs impair cell cycle progression and drive apoptosis. Many essential lncRNAs demonstrate dynamic expression across tissues during development. Using ~9,000 primary tumors, we pinpoint those lncRNAs whose expression in tumors correlates with survival, yielding new biomarkers and potential therapeutic targets. This transcriptome-wide survey of functional lncRNAs advances our understanding of noncoding transcripts and demonstrates the potential of transcriptome-scale noncoding screens with Cas13.

2026-04-01 | GSE326230 | GEO

Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells

Project description:Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using massively parallel RNA-targeting CRISPR Cas13 screens, we probed how loss of ~6,200 lncRNAs impacts cell fitness across five human cell lines and identified 778 lncRNAs with either context-specific or broad essentiality. We observe a high level of consistency between distinct guide RNAs targeting the same lncRNA in the pooled screens and confirm their essentiality with individual perturbations. We find that the overwhelming majority of essential lncRNAs operate independently of their nearest protein-coding genes. Using transcriptome profiling in single cells, we discover that essential lncRNAs modulate key cellular pathways for proliferation and that their loss can impair cell cycle progression and drive apoptosis. Many essential lncRNAs demonstrate dynamic expression across tissues during development and, using ~9,000 primary tumors, we pinpoint those lncRNAs whose expression in tumors correlates with survival, yielding new biomarkers and potential therapeutic targets. This transcriptome-wide survey of functional lncRNAs advances our understanding of noncoding transcripts and demonstrates the potential of transcriptome-scale noncoding screens with Cas13.

2024-11-15 | GSE281460 | GEO

Precise RNA targeting with CRISPR-Cas13d

Project description:The possibility of collateral RNA degradation poses a concern for transcriptome perturbations and therapeutic applications using CRISPR-Cas13. We show that collateral activity only occurs with high RfxCas13d expression. Using low-copy RfxCas13d in transcriptome-scale and combinatorial pooled screens, we achieve high on-target knockdown without extensive collateral activity. Further, analysis of a high-fidelity Cas13 variant suggests that its reduced collateral activity may be due to overall diminished nuclease capability.

2024-12-18 | GSE284017 | GEO

Transcriptome Analyses of LncRNA Metabolic Regulators from High Fat Diet Induced T2DM Mouse Adipose Tissue

Project description:To search long noncoding RNAs (lncRNAs) which regulating energy metabolism in high fat diet induced T2DM mouse, we performed transcriptome analyses to simultaneously profile mRNAs and lncRNAs in epididymal adipose tissue in normal and high fat diet induced mouse. Combining genome-wide screens, bioinformatics function predictions, and cell-based analyses, we developed an integrative roadmap to identify lncRNA metabolic regulators in epididymal adipose tissue under high fat diet induced T2DM mouse.

2019-06-01 | GSE100028 | GEO

Reframing gene essentiality in terms of adaptive flexibility

Project description:Essentiality assays are commonly practiced as important tools for the discovery of gene functions. Growth/no growth screens of single gene knockout strain collections are often utilized to test the predictive power of genome-scale models. False positive predictions occur when computational analysis predicts a gene to be non-essential, however experimental screens deem the gene to be essential. One explanation for this inconsistency is that the model contains the wrong information, possibly an incorrectly annotated alternative pathway or isozyme reaction. Inconsistencies could also be attributed to experimental limitations, such as growth tests with arbitrary time cut-offs. The focus of this study was to resolve such inconsistencies to better understand isozyme activities and gene essentiality. Gene-deletion strains associated with false positive predictions of gene essentiality on defined minimal medium for Escherichia coli were targeted for extended growth tests followed by population sequencing.

2018-07-19 | GSE117303 | GEO

Homo sapiens

Project description:Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells

| PRJNA1161603 | ENA

LETR1 (LINC01197) RNA pull-down in human LECs followed by LC-MSMS

Project description:Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determined, for the first time, the global lineage-specific lncRNAome of human dermal blood and lymphatic endothelial cells (BECs and LECs), combining RNA-Seq and CAGE-Seq. A subsequent genome-wide antisense oligonucleotide-knockdown profiling of two BEC- and two LEC-specific lncRNAs identified LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA and RNA-protein interaction studies, and phenotype rescue analyses revealed that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes governing the growth and migratory ability of LECs. Together, our study provides new evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.

2020-12-21 | PXD018578 | Pride

Identification of Functional Regulatory Elements in the Human Genome Using Pooled CRISPR Screens

Project description:Genome-scale pooled CRISPR screens are powerful tools for identifying genetic dependencies across varied cellular processes. The vast majority of CRISPR screens reported to date have focused exclusively on the perturbation of protein-coding gene function. However, protein-coding genes comprise <2% of the sequence space in the human genome leaving a substantial portion of the genome uninterrogated. Noncoding regions of the genome harbor important regulatory elements (e.g. promoters, enhancers, suppressors) that influence cellular processes but high-throughput methods for evaluating their essentiality have yet to be established. Here, we describe a CRISPR-based screening approach that facilitates the functional profiling of thousands of noncoding regulatory elements in parallel. We selected the tumor suppressor p53 as a model system and designed a pooled CRISPR library targeting thousands of p53 binding sites throughout the genome. Following transduction into dCas9-KRAB-expressing cells we identified several regulatory elements that influence cell proliferation. Moreover, we uncovered multiple elements that are required for the p53-mediated DNA damage response. Surprisingly, many of these elements are located deep within intergenic regions of the genome that have no prior functional annotations. This work diversifies the applications for pooled CRISPR screens and provides a framework for future functional studies focused on noncoding regulatory elements.

2019-08-21 | GSE126320 | GEO

A genome-wide long noncoding RNA CRISPRi screen identifies PRANCR as a novel regulator of epidermal homeostasis

Project description:Long noncoding RNAs (lncRNAs) are a major component of the noncoding genome, but their functions in human development and disease are still incompletely understood. CRISPR interference screens allow for systematic identification of functional lncRNAs that regulate fundamental biological processes such as tissue development and homeostasis. We identified 2,263 lncRNAs transcribed in human epidermis, and performed a comprehensive CRISPR interference screen against all these elements in primary human epidermal progenitors. Our screen identified 209 lncRNAs controlling epidermal progenitor renewal, with the majority (94%) being positive regulators of proliferation. To validate the results, we performed deeper characterization of a novel lncRNA identified from this screen, PRANCR (LINC01481), using RNA interference-mediated transcript knockdown and phenotype analysis in organotypic human tissue. PRANCR depletion inhibited progenitor proliferation through a G2/M cell cycle arrest, reduced clonogenic potential, and impaired functional epidermal stratification. Transcriptome and computational analysis indicated that PRANCR governs progenitor renewal by controlling the expression of 1,136 genes in trans, in part via the p53-E2F4-CHR pathway. This pathway controls the expression of G2/M cell cycle genes and is a novel mechanism of regulating cell proliferation in epidermal progenitors.

2019-11-07 | GSE125400 | GEO

Pulldown of proteins interacting with SGOL1-AS1 in AML

Project description:Epigenetic dysregulation is a common feature of acute myeloid leukemia (AML). Recently it has become clear that long noncoding RNAs (lncRNAs) can play a key role in epigenetic regulation, and consequently also dysregulation. Currently, our understanding of the requirements and roles of lncRNAs in AML is still limited. Using CRISPRi screening, we identified the lncRNA SGOL1-AS1 as an essential regulator of survival in THP-1 AML cells. We use RNA affinity purification using a biotinylated bait to pull down binding partners of the lncRNA, SGOL1-AS1. The identified proteins show a signficant enrichment for chromatin-modifying proteins involved in gene repression and chromosome organization.

2023-06-12 | PXD034329 | 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