Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3' splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3' splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinc...Continue Reading
Identification, purification, and biochemical characterization of U2 small nuclear ribonucleoprotein auxiliary factor
A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles
AU-rich elements and alternative splicing in the beta-catenin 3'UTR can influence the human beta-catenin mRNA stability
RNA interference knockdown of hU2AF35 impairs cell cycle progression and modulates alternative splicing of Cdc25 transcripts
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation
The U2AF35-related protein Urp contacts the 3' splice site to promote U12-type intron splicing and the second step of U2-type intron splicing
Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients
Deep sequencing of the T-cell receptor repertoire in CD8+ T-large granular lymphocyte leukemia identifies signature landscapes.
Integrative DNA methylome analysis of pan-cancer biomarkers in cancer discordant monozygotic twin-pairs
Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease
In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities
A nutrient combination designed to enhance synapse formation and function improves outcome in experimental spinal cord injury
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells
Elucidating Genomic Characteristics of Lung Cancer Progression from In Situ to Invasive Adenocarcinoma
Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival
Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis
Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems
Nanopore long-read RNAseq reveals widespread transcriptional variation among the surface receptors of individual B cells
Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks
Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.
Circ-U2AF1 promotes human glioma via derepressing neuro-oncological ventral antigen 2 by sponging hsa-miR-7-5p
The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation
Risk stratification for lung adenocarcinoma on EGFR and TP53 mutation status, chemotherapy, and PD-L1 immunotherapy
Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis
Myeloid Disease Mutations of Splicing Factor SRSF2 Cause G2-M Arrest and Skewed Differentiation of Human Hematopoietic Stem and Progenitor Cells
Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease
Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia
Widespread Separation of the Polypyrimidine Tract From 3' AG by G Tracts in Association With Alternative Exons in Metazoa and Plants
Myelodysplastic Syndrome-Associated SRSF2 Mutations Cause Splicing Changes by Altering Binding Motif Sequences
U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies
An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications
Alternative splicing and cancer: insights, opportunities, and challenges from an expanding view of the transcriptome.
Impaired hematopoiesis and leukemia development in mice with a conditional knock-in allele of a mutant splicing factor gene U2af1
Aberrant RNA Splicing Events Driven by Mutations of RNA-Binding Proteins as Indicators for Skin Cutaneous Melanoma Prognosis
Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays
Spliceosome Mutations Induce R Loop-Associated Sensitivity to ATR Inhibition in Myelodysplastic Syndromes
U2AF1 expression is a novel and independent prognostic indicator of childhood T-lineage acute lymphoblastic leukemia
A functional network of gastric-cancer-associated splicing events controlled by dysregulated splicing factors.
Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.
AML: Role of LSD1 by CRISPR (Keystone)
Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.
Acute Myeloid Leukaemia & RNA
Acute myeloid leukaemia (AML) is a common hematological type of cancer. As the population ages, there has been a rise in the frequency of AML. RNA expression has been used to see if there are different genetic profiles that exist within AML and whether these may underpin the variations in survival rates. Here is the latest research on AML and RNA.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.
B-Cell Leukemia (Keystone)
B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.
A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.
Cancer Genomics (Keystone)
Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.