Repressing the neuron within.
A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre-mRNAs encoding neuronal-specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track-binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal genes are turned on in both non-neuronal and neuronal cells, restricted expression of PTB in non-neuronal cells diverts their mRNAs to nonsense-mediated decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron.
18 references, click to expand
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Coordinate repression of a trio of neuron-specific splicing events by the splicing regulator PTB.RNA. 1999 Jan;5(1):117-30 PMID: 9917071
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MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development.Genes Dev. 2007 Jan 1;21(1):71-84 PMID: 17210790
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The splice of life: alternative splicing and neurological disease.Nat Rev Neurosci. 2001 Jan;2(1):43-50 PMID: 11253358
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A brain-specific microRNA regulates dendritic spine development.Nature. 2006 Jan 19;439(7074):283-9 PMID: 16421561
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The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing.Mol Cell. 2007 Aug 3;27(3):435-48 PMID: 17679093
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The spliceosome: no assembly required?Mol Cell. 2002 Jan;9(1):8-9 PMID: 11804581
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RNA binding proteins and the regulation of neuronal synaptic plasticity.Curr Opin Neurobiol. 2006 Feb;16(1):102-10 PMID: 16418001
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Intronic binding sites for hnRNP A/B and hnRNP F/H proteins stimulate pre-mRNA splicing.PLoS Biol. 2006 Feb;4(2):e21 PMID: 16396608
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MicroRNA: microRNAs reach out into dendrites.Curr Biol. 2006 Feb 21;16(4):R121-3 PMID: 16488859
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RNA binding specificity of hnRNP proteins: a subset bind to the 3' end of introns.EMBO J. 1988 Nov;7(11):3519-29 PMID: 3208740
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A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons.Genes Dev. 2007 Jul 1;21(13):1636-52 PMID: 17606642
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A neuron-specific splicing switch mediated by an array of pre-mRNA repressor sites: evidence of a regulatory role for the polypyrimidine tract binding protein and a brain-specific PTB counterpart.RNA. 1997 Sep;3(9):996-1015 PMID: 9292499
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Novel modes of splicing repression by PTB.Trends Biochem Sci. 2006 Feb;31(2):73-6 PMID: 16403634
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A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing.Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6350-5 PMID: 10829067
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Neuronal proteins custom designed by alternative splicing.Curr Opin Neurobiol. 2005 Jun;15(3):358-63 PMID: 15961039
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Alternative pre-mRNA splicing and neuronal function.Prog Mol Subcell Biol. 2003;31:187-216 PMID: 12494767
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Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein.Mol Cell Biol. 2000 Oct;20(20):7463-79 PMID: 11003644
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Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1.Mol Cell. 2007 Aug 3;27(3):420-34 PMID: 17679092
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