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1.
Trends Neurosci ; 30(1): 1-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17116335

ABSTRACT

GABA, a major inhibitory neurotransmitter in the adult brain, activates synaptic and extrasynaptic GABA(A) receptors, causing hyperpolarization of mature neurons. As in the embryonic nervous system, GABA depolarizes neural progenitors and immature neurons in the adult brain. Several recent studies have suggested that GABA has crucial roles in regulating different steps of adult neurogenesis, including proliferation of neural progenitors, migration and differentiation of neuroblasts, and synaptic integration of newborn neurons. Here, we review recent findings on how GABA regulates adult neurogenesis in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. We also discuss an emerging view that GABA serves as a key mediator of neuronal activity in setting the tempo of adult neurogenesis.


Subject(s)
Cell Differentiation/physiology , Nervous System/embryology , Neurons/cytology , gamma-Aminobutyric Acid/metabolism , Animals , Cell Movement , Cell Proliferation , Hippocampus/cytology , Lateral Ventricles/cytology , Models, Biological , Neurons/physiology
2.
Mol Cell Biol ; 24(14): 6241-52, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15226427

ABSTRACT

RNA polymerase II (Pol II) termination is triggered by sequences present in the nascent transcript. Termination of pre-mRNA transcription is coupled to recognition of cis-acting sequences that direct cleavage and polyadenylation of the pre-mRNA. Termination of nonpolyadenylated [non-poly(A)] Pol II transcripts in Saccharomyces cerevisiae requires the RNA-binding proteins Nrd1 and Nab3. We have used a mutational strategy to characterize non-poly(A) termination elements downstream of the SNR13 and SNR47 snoRNA genes. This approach detected two common RNA sequence motifs, GUA[AG] and UCUU. The first motif corresponds to the known Nrd1-binding site, which we have verified here by gel mobility shift assays. We also show that Nab3 protein binds specifically to RNA containing the UCUU motif. Taken together, our data suggest that Nrd1 and Nab3 binding sites play a significant role in defining non-poly(A) terminators. As is the case with poly(A) terminators, there is no strong consensus for non-poly(A) terminators, and the arrangement of Nrd1p and Nab3p binding sites varies considerably. In addition, the organization of these sequences is not strongly conserved among even closely related yeasts. This indicates a large degree of genetic variability. Despite this variability, we were able to use a computational model to show that the binding sites for Nrd1 and Nab3 can identify genes for which transcription termination is mediated by these proteins.


Subject(s)
Gene Expression Regulation, Fungal , RNA Precursors/metabolism , RNA, Small Nucleolar/genetics , Saccharomyces cerevisiae/genetics , Terminator Regions, Genetic , Base Sequence , Fungal Proteins/genetics , Fungal Proteins/metabolism , Molecular Sequence Data , Mutation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Polyadenylation , Protein Binding , RNA Polymerase II/metabolism , RNA Precursors/genetics , RNA Processing, Post-Transcriptional , RNA, Small Nucleolar/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism
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