Transcriptomics

Dataset Information

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Alternative Splicing in Erythropoiesis


ABSTRACT: Differentiating erythroid cells execute a unique gene expression program that insures synthesis of the appropriate proteome at each stage of maturation. Standard expression microarrays provide important insight into erythroid gene expression, but cannot detect qualitative changes in transcript structure, mediated by RNA processing, that alter structure and function of encoded proteins. We analyzed stage-specific changes in the late erythroid transcriptome via use of high resolution microarrays that detect altered expression of individual exons. Ten differentiation-associated changes in erythroblast splicing patterns were identified, including the previously known activation of protein 4.1R exon 16 splicing. Six new alternative splicing switches involving enhanced inclusion of internal cassette exons were discovered, as well as three changes in use of alternative first exons. All of these erythroid stage-specific splicing events represent activated inclusion of authentic annotated exons, suggesting they represent an active regulatory process rather than a general loss of splicing fidelity. The observation that three of the regulated transcripts encode RNA binding proteins (SNRP70, HNRPLL, MBNL2) may indicate significant changes in the RNA processing machinery of late erythroblasts. Together these results support the existence of a regulated alternative pre-mRNA splicing program that is critical for late erythroid differentiation. Keywords: Time course; Splicing-sensitive microarray For Exon array hybridizations: 3 biological replicates of day 7, 2 biological replicates of day 10, 3 biological replicates of day 14; For HJAY array hybridizations: 5 biological replicates each were analyzed from day 7 and day 14. One day 14 replicate was deemed an outlier and removed from subsequent analyses.

ORGANISM(S): Homo sapiens  

SUBMITTER: Anthony C Schweitzer  John G Conboy   Tyson A Clark   Jeong-Ah Kang   Amittha Wickrema   Sherry L Gee   Miki L Yamamoto   Jason Wray Hubbard    

PROVIDER: E-GEOD-14588 | ArrayExpress | 2010-05-16

SECONDARY ACCESSION(S): GSE14588PRJNA111707

REPOSITORIES: GEO, ArrayExpress

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Publications

Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis.

Yamamoto Miki L ML   Clark Tyson A TA   Gee Sherry L SL   Kang Jeong-Ah JA   Schweitzer Anthony C AC   Wickrema Amittha A   Conboy John G JG  

Blood 20090204 14


Differentiating erythroid cells execute a unique gene expression program that insures synthesis of the appropriate proteome at each stage of maturation. Standard expression microarrays provide important insight into erythroid gene expression but cannot detect qualitative changes in transcript structure, mediated by RNA processing, that alter structure and function of encoded proteins. We analyzed stage-specific changes in the late erythroid transcriptome via use of high-resolution microarrays th  ...[more]

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