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U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3’ End Formation

ABSTRACT: We sequenced mRNA from Ba/F3 cells with U2AF35(S34F) expressing or parental Ba/F3

ORGANISM(S): Mus musculus

PROVIDER: GSE63404 | GEO | 2016/05/01

SECONDARY ACCESSION(S): PRJNA267679

REPOSITORIES: GEO

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U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 3' End Formation.

Project description:Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy-related factor 7 (Atg7) pre-mRNA is abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity.

| S-EPMC5012111 | biostudies-literature

Identification of functional genetic variants in transformed Ba/F3 cells expressing U2AF35(S34F)

Project description:Identification of functional genetic variants in transformed Ba/F3 cells expressing U2AF35(S34F)

| PRJNA473584 | ENA

Expression analysis of mutant U2AF35 transduced cells

Project description:In this study, to obtain the biological impact of the mutated U2AF35, HeLa and TF-1 cells were retrovirally transduced with either mock, wild-type or S34F mutant of U2AF35, and Expression array was performed. Expression analysis was performed for mock, wild-type U2AF35 or S34F mutant transduced HeLa and MDS-derived TF-1 cell line in triplicate.

2011-09-11 | E-GEOD-31172 | biostudies-arrayexpress

Exon level expression profiling of mutant U2AF35 transduced HeLa cells

Project description:In this study, to obtain the biological impact of the mutated U2AF35, HeLa cells were retrovirally transduced with either mock, wild-type or S34F mutant of U2AF35, and Exon array was performed. Exon level analysis was performed for mock, wild-type U2AF35 or S34F mutant transduced HeLa in triplicate.

2011-09-11 | E-GEOD-31171 | biostudies-arrayexpress

Expression analysis of mutant U2AF35 transduced cells

2011-09-12 | GSE31172 | GEO

Exon level expression profiling of mutant U2AF35 transduced HeLa cells

2011-09-12 | GSE31171 | GEO

Expression profile of mutant U2AF35 transduced cells

Project description:This SuperSeries is composed of the following subset Series: GSE31171: Exon level expression profiling of mutant U2AF35 transduced HeLa cells GSE31172: Expression analysis of mutant U2AF35 transduced cells Refer to individual Series

2012-04-09 | E-GEOD-31173 | biostudies-arrayexpress

Effect of U2AF1-S34F mutation in mouse neutrophils

Project description:To investigate the effect of the MDS-associated U2AF1-S34F mutation on gene expression and pre-mRNA splicing in mouse neutrophils, we performed RNA-seq on RNA isolated from bone marrow neutrophils expressing either U2AF1-S34F or U2AF1-WT transgenes

2024-08-26 | GSE209799 | GEO

Identification of differentially spliced genes by wild type or S34F mutation of U2AF1

Project description:Identification of differentially spliced genes by wild type or S34F mutation of U2AF1 Examination of effects on splicing events by overexpressing wipdtype or S34F mutation of two U2AF1 isoforms in A549 cells. All experimental conditions are performed in duplicate.

2015-11-01 | E-GEOD-66553 | biostudies-arrayexpress

Murine Ba/F3 Cells: Ba/F3 cells expressing wild type JAK2 (WT cells) vs. Ba/F3 cells expressing JAK2 V617F mutant (VF cells)

Project description:Transcriptional profiling of transformed Ba/F3 cells by myeloproliferative neoplasm-associated JAK2 V617F mutant comparing control Ba/F3 cells expressing wild type JAK2.

2013-10-31 | GSE34239 | GEO

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