Back to Search
Start Over
Cross-Regulation between an Alternative Splicing Activator and a Transcription Repressor Controls Neurogenesis
- Source :
- Molecular Cell. 43(5):843-850
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Neurogenesis requires the concerted action of numerous genes that are regulated at multiple levels. However, how different layers of gene regulation are coordinated to promote neurogenesis is not well understood. We show that the neural-specific Ser/Arg repeat-related protein of 100 kDa (nSR100/SRRM4) negatively regulates REST (NRSF), a transcriptional repressor of genes required for neurogenesis. nSR100 directly promotes alternative splicing of REST transcripts to produce a REST isoform (REST4) with greatly reduced repressive activity, thereby activating expression of REST targets in neural cells. Conversely, REST directly represses nSR100 in nonneural cells to prevent the activation of neural-specific splicing events. Consistent with a critical role for nSR100 in the inhibition of REST activity, blocking nSR100 expression in the developing mouse brain impairs neurogenesis. Our results thus reveal a fundamental role for direct regulatory interactions between a splicing activator and transcription repressor in the control of the multilayered regulatory programs required for neurogenesis.
- Subjects :
- Gene isoform
Transcription, Genetic
Neurogenesis
RNA Splicing
Mice, Inbred Strains
Nerve Tissue Proteins
Biology
Mice
Transcription (biology)
Animals
Protein Isoforms
Gene
Molecular Biology
Cells, Cultured
Neurons
Regulation of gene expression
Activator (genetics)
Alternative splicing
Cell Biology
Cell biology
Repressor Proteins
Alternative Splicing
RNA splicing
Cancer research
Transcription Factors
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 43
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....5861f8c3fccb6fbc07ff34b0877222b8
- Full Text :
- https://doi.org/10.1016/j.molcel.2011.08.014