BC1 and BC200 RNA: Sequence and transcriptional analysis.
Item
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Title
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BC1 and BC200 RNA: Sequence and transcriptional analysis.
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Identifier
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AAI9304701
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identifier
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9304701
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Creator
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Martignetti, John Attilio.
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Contributor
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Adviser: Jurgen Brosius
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Date
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1992
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Neuroscience | Biology, Genetics
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Abstract
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Rodent BC1 RNA and primate BC200 RNA are tissue specific, nontranslatable small cytoplasmic RNAs representing the first examples of neural specific RNA polymerase III transcribed products. BC1 RNA is believed to have evolved via a tRNA{dollar}\sp{lcub}\rm Ala{rcub}{dollar} and BC200 RNA via 7SL RNA. Despite their seemingly unrelated phylogenetic origins, these two molecules share a similar tripartite structure and limited sequence identity in their 3{dollar}\sp\prime{dollar} ends. Furthermore, these RNAs, in the form of ribonucleoprotein complexes (RNP), are present not only in the somatic but also the dendritic compartments of analogous subsets of neurons. These results coupled with BC1 RNA's expression coinciding with developmental synaptogenesis and BC200 RNA's ability to bind two protein subunits of the signal recognition particle suggests that BC1 and BC200 RNAs may be involved in postsynaptic protein biosynthesis.;The first part of this work identified, sequenced and analyzed the genes encoding BC1 RNA from several rodent species, including rat, mouse, Chinese hamster and guinea pig, and human BC200 RNA. Additionally, a number of BC1 and BC200 RNA pseudogenes were also characterized. Analysis of the rodent sequences reveals that although BC1 RNA is of a relatively recent phylogenetic origin, evolutionary pressure has existed to conserve the genes and their neural specific expression for at least 55 million years. Also demonstrated is that the human BC200 RNA gene and its RNA product, respectively, represent the only known transcriptionally active Alu element and the first example of a primate RNA polymerase III transcribed neural specific RNA. Furthermore, the BC200 RNA gene provides the first evidence of transcriptionally active monomeric Alu elements: possible progenitors to the nearly half million Alu sequences found dispersed throughout the human genome.;The second aspect of this work was the analysis of the transcriptional regulation of the BC1 RNA gene. For in vivo studies, several transgenic mouse lines were established. For in vitro studies, a novel homologous whole cell extract, prepared from rat brain tissue, capable of supporting RNA polymerase III (pol III) catalyzed transcription was developed. Using this extract, functional polymerase II and polymerase III promoter elements involved in regulating rat BC1 RNA transcription were defined. Moreover, a variant pol III promoter, able to "communicate" with pol II promoters was identified. This suggests a novel mechanism by which the BC1 RNA gene and possibly other pol III transcribed genes can interact with pol II factors to be differentially regulated.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
