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| 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
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| 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.
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| Overall design |
PTBP1 siRNA, PTBP1+PTBP2 siRNA, or control siRNA
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| 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.
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| Department |
Bioinformatics
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| Street address |
1 DNA Way
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| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA165651 |
| SRA |
SRP013051 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE37933_gene_levels.tsv.gz |
1.2 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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