Nova regulates brain-specific splicing to shape the synapse

Alternative RNA splicing greatly increases proteome diversity and may thereby contribute to tissue-specific functions. We carried out genome-wide quantitative analysis of alternative splicing using a custom Affymetrix microarray to assess the role of the neuronal splicing factor Nova in the brain. We used a stringent algorithm to identify 591 exons that were differentially spliced in the brain relative to immune tissues, and 6.6% of these showed major splicing defects in the neocortex of Nova2-/- mice. We tested 49 exons with the largest predicted Nova-dependent splicing changes and validated all 49 by RT-PCR. We analyzed the encoded proteins and found that all those with defined brain functions acted in the synapse (34 of 40, including neurotransmitter receptors, cation channels, adhesion and scaffold proteins) or in axon guidance (8 of 40). Moreover, of the 35 proteins with known interaction partners, 74% (26) interact with each other. Validating a large set of Nova RNA targets has led us to identify a multi-tiered network in which Nova regulates the exon content of RNAs encoding proteins that interact in the synapse.     

Heartwood constituents ofPinus formosana

Zusammenfassung Die Untersuchung der sauren Anteile eines Extraktes des Kernholzes vonPinus formosana zeigte das Vorhandensein von Pinostrobin und Tectochrysin neben Dehydroabietin- und Isodextroprimarsäure. Diese Befunde erlauben,P. formosana der Gruppe Haploxylon zuzuteilen.     

Extra-embryonic function of Rb is essential for embryonic development and viability

The retinoblastoma (Rb) gene was the first tumour suppressor identified. Inactivation of Rb in mice results in unscheduled cell proliferation, apoptosis and widespread developmental defects, leading to embryonic death by day 14.5 (refs 2-4). However, the actual cause of the embryonic lethality has not been fully investigated. Here we show that loss of Rb leads to excessive proliferation of trophoblast cells and a severe disruption of the normal labyrinth architecture in the placenta. This is accompanied by a decrease in vascularization and a reduction in placental transport function. We used two complementary techniques-tetraploid aggregation and conditional knockout strategies-to demonstrate that Rb-deficient embryos supplied with a wild-type placenta can be carried to term, but die soon after birth. Most of the neurological and erythroid abnormalities thought to be responsible for the embryonic lethality of Rb-null animals were virtually absent in rescued Rb-null pups. These findings identify and define a key function of Rb in extra-embryonic cell lineages that is required for embryonic development and viability, and provide a mechanism for the cell autonomous versus non-cell autonomous roles of Rb in development.     

Similarity of teleocidin B and phorbol ester tumour promoters in effects on membrane receptors

The tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and structurally related phorbol esters effect changes in avian and mammalian cell cultures that mimic transformation by oncogenic viruses or chemical carcinogens and the inhibition or induction of various types of differentiation (for review see refs 1--3). Unlike initiating carcinogens, which seem to act by binding covalently to cellular DNA, the primary site of action of the phorbol ester tumour promoters seems to be the cell membrane; indeed, specific high-affinity saturable receptors for phorbol esters have been identified in cell membranes. The recently discovered class of tumour promoters, the teleocidins, are as potent as TPA in the induction of ornithine decarboxylase in mouse skin, the inhibition of differentiation of Friend erythroleukaemia cells, the induction of HL-60 cell adhesion and the promotion of tumours on mouse skin. As the teleocidins are structurally unrelated to the phorbol esters, we set out to determine their effects on cell membranes and receptors. We found that in rodent cell cultures, teleocidin B and dihydroteleocidin B have effects similar to those of TPA and that, at nanomolar concentrations, teleocidin inhibits the binding of phorbol esters to cell-surface receptors, which suggests that the action of both classes of compounds may be mediated by the same or a similar receptor system.     

On the relationship between glucagon and secretin

Zusammenfassung Die Polypeptidhormone Glukagon und Sekretin wurden auf der Basis des genetischen Codes verglichen. Es wurde daraus geschlossen, dass die beiden Substanzen ursprünglich von einem gemeinsamen Gen erzeugt wurden.

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This investigation was supported by the National Science Foundation (No. GB-3208) and the National Institutes of Health (No. AM 10671-01).