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Glioblastoma (GBM) is a devastating malignancy with few therapeutic options. We identify PRMT5 in an in vivo GBM shRNA screen and show that PRMT5 knockdown or inhibition potently suppresses in vivo GBM tumors, including patient-derived xenografts. Pathway analysis implicates splicing in cellular PRMT5 dependency, and we identify a biomarker that predicts sensitivity to PRMT5 inhibition. We find that PRMT5 deficiency primarily disrupts the removal of detained introns (DIs). This impaired DI splicing affects proliferation genes, whose downregulation coincides with cell cycle defects, senescence and/or apoptosis. We further show that DI programs are evolutionarily conserved and operate during neurogenesis, suggesting that they represent a physiological regulatory mechanism. Collectively, these findings reveal a PRMT5-regulated DI-splicing program as an exploitable cancer vulnerability.
Pubmed ID: 28966034 RIS Download
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Collection of pathways and pathway annotations. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways (signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism) . Provides website to navigate pathway knowledge and a suite of data analysis tools to support the pathway-based analysis of complex experimental and computational data sets.
View all literature mentionsSoftware tool as a framework for modeling the sequences of short sequence motifs based on the maximum entropy principle (MEP). Used for sequence motifs such as those involved in RNA splicing.
View all literature mentionsThis unknown targets Symmetric Di-Methyl Arginine Motif
View all literature mentionsThis polyclonal targets c-Raf
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis polyclonal targets Histone H4 (symmetric di methyl R3) antibody - ChIP Grade
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets rat IgG HRP-linked
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets eIF4E
View all literature mentionsThis polyclonal targets SNRPD3 antibody produced in rabbit
View all literature mentionsThis unknown targets Human SNRPN
View all literature mentionsThis monoclonal targets AURKB
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Skb1Hs methyltransferase
View all literature mentionsThis monoclonal targets Hsp90
View all literature mentionsCell line CAL-33 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW1783 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line C2BBe1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ZR-75-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LN-18 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MeWo is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-MEL-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WM266-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-138MG is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LN-229 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-172 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CCD-1112Sk is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line PANC-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line T98G is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsProgramming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsSoftware package focused on finding differential exon usage using RNA-seq exon counts between samples with different experimental designs. It provides functions that allows the user to make the necessary statistical tests based on a model that uses the negative binomial distribution to estimate the variance between biological replicates and generalized linear models for testing. The package also provides functions for the visualization and exploration of the results.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 30,2023. Software for differential gene expression analysis based on the negative binomial distribution. It estimates variance-mean dependence in count data from high-throughput sequencing assays and tests for differential expression.
View all literature mentionsWeb application to generate sequence logos, graphical representations of patterns within multiple sequence alignment. Designed to make generation of sequence logos easy. Sequence logo generator.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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