Christopher W. J. Smith

Learn More
In violation of the 'one gene, one polypeptide' rule, alternative splicing allows individual genes to produce multiple protein isoforms - thereby playing a central part in generating complex proteomes. Alternative splicing also has a largely hidden function in quantitative gene control, by targeting RNAs for nonsense-mediated decay. Traditional gene-by-gene(More)
Polypyrimdine tract binding protein (PTB) is a regulator of alternative splicing, mRNA 3' end formation, mRNA stability and localization, and IRES-mediated translation. Transient overexpression of PTB can influence alternative splicing, sometimes resulting in nonphysiological splicing patterns. Here, we show that alternative skipping of PTB exon 11 leads to(More)
BACKGROUND Neurocognitive deficits are considered to be central to the pathophysiology of schizophrenia, and the neurodevelopmental model suggests that such deficits precede full-blown psychosis. The present study examined performance on a broad neuropsychological battery of young subjects considered to be at clinical high risk for schizophrenia, who were(More)
Among the targets of the repressive splicing regulator, polypyrimidine tract binding protein (PTB) is its own pre-mRNA, where PTB-induced exon 11 skipping produces an RNA substrate for nonsense-mediated decay (NMD). To identify additional PTB-regulated alternative splicing events, we used quantitative proteomic analysis of HeLa cells after knockdown of PTB.(More)
Despite the widespread acceptance of the neurodevelopmental model of schizophrenia, its application to research concerned with the prodromal phase of illness is limited. Little recognition has been given to the concept of an enduring biological vulnerability to illness that may be responsive to early intervention. Rather, the focus of most prodromal studies(More)
INTRODUCTION Research on prediction and prevention of schizophrenia has increasingly focused on prodromal (prepsychosis) social and role dysfunction as developmentally early, stable, and treatment-resistant illness components. In this report, 2 new measures, Global Functioning: Social and Global Functioning: Role, are presented, along with preliminary(More)
To gain global insights into the role of the well-known repressive splicing regulator PTB, we analyzed the consequences of PTB knockdown in HeLa cells using high-density oligonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of(More)
As part of an investigation of the functional mechanics of the hind wing of the desert locust Schistocerca gregaria, the Young's modulus of the membrane was measured using a newly developed universal materials test machine capable of testing very small specimens of cuticle, down to 1 mm gauge length. Strain was measured optically. Specimens were cut from(More)
Alternative splicing (AS) strongly affects gene expression by generating protein isoform diversity. However, up to one-third of human AS events create a premature termination codon that would cause the resulting mRNA to be degraded by nonsense-mediated mRNA decay (NMD). The extent to which such events represent functionally selected post-transcriptional(More)
Regulated switching of the mutually exclusive exons 2 and 3 of alpha-tropomyosin (TM) involves repression of exon 3 in smooth muscle cells. Polypyrimidine tract-binding protein (PTB) is necessary but not sufficient for regulation of TM splicing. Raver1 was identified in two-hybrid screens by its interactions with the cytoskeletal proteins actinin and(More)