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Series GSE37933 Query DataSets for GSE37933
Status Public on Jul 12, 2012
Title Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Differentiated cells acquire unique structural and functional traits through coordinated expression of lineage-specific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and non-neuronal cells. However, in non-neuronal cells, the splicing of 3’-terminal introns within these genes is repressed by polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these intron-containing transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery including the nuclear pore-associated protein Tpr and components of the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context.
Overall design PTBP1 siRNA, PTBP1+PTBP2 siRNA, or control siRNA
Contributor(s) Yap K, Lim ZQ, Khandelia P, Friedman BA, Makeyev EV
Citation(s) 22661231, 30053257, 25375251
Submission date May 11, 2012
Last update date Oct 22, 2019
Contact name Brad A Friedman
Organization name Genentech, Inc.
Department Bioinformatics
Street address 1 DNA Way
City South San Francisco
State/province CA
ZIP/Postal code 94080
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (3)
GSM930225 Control siRNA
GSM930226 PTBP1 siRNA
GSM930227 PTBP1+PTBP2 siRNAs
BioProject PRJNA165651
SRA SRP013051

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Supplementary file Size Download File type/resource
GSE37933_gene_levels.tsv.gz 1.2 Mb (ftp)(http) TSV
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Processed data are available on Series record

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