BC1 and BC200scRNAs: Regulation of RNA polymerase III transcription in neurons and deregulation during tumorigenesis.
Item
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Title
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BC1 and BC200scRNAs: Regulation of RNA polymerase III transcription in neurons and deregulation during tumorigenesis.
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Identifier
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AAI9510646
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identifier
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9510646
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Creator
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Chen, Wei.
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Contributor
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Adviser: Jurgen Brosius
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Date
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1994
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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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Chemistry, Biochemistry | Biology, Molecular | Biology, Neuroscience
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Abstract
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BC1 and BC200 are neuron specific cytoplasmic small RNAs conserved in rodents and primates, respectively. These two small RNAs come from different progenitors with different primary sequences, but they share several common characteristics. First, three similar domains are contained in the structures of BC1 and BC200 RNAs. Second, both RNAs are the first known RNA polymerase III transcripts with neuronal specific regulation. Third, the subcellular location of both RNAs is very similar; they have been identified in somatic and dendritic compartments of neurons. Fourth, both RNAs are part of a ribonucleoprotein complex (RNP). It has been hypothesized that BC1 and BC200 RNAs might be involved in regulation of local postsynaptic protein biosynthesis in dendrites of nerve cells.;The main aspect of this work was to begin to elucidate the molecular mechanism which is responsible for the neuron-specific regulation of BC1 RNA. Transgenic mice carrying 1.4kb and 1kb (357bp including two octamer motifs were deleted at the 5{dollar}\sp\prime{dollar} end of the 1.4kb fragment) rat BC1 gene constructs have been studied. Both 1.4kb and 1kb transgenic mice expressed the transgene-encoded rat BC1 RNA in the nervous system but not in other tissues. Transgene BC1 RNA also has been detected in a subset of neurons where it is located in somatic and/or dendritic domains. Comparing these two constructs, we found that the levels of expression per transgene copy of deletion construct is about 5 times less than with the 1.4kb construct. In addition, the integration site-independence disappeared in the transgenic mice harboring the 1kb construct. We conclude that cis-acting regulatory elements, subject to neuron-specific control, are located within the 1kb construct of the rat BC1 RNA gene. Sequences in the 357bp deleted fragment might be candidates for elements responsible for transcriptional enhancement.;The second aspect of this work was to investigate the transcriptional regulation of both BC1 and BC200 RNAs during tumorigenesis. These studies first demonstrated that both BC1 and BC200 RNAs are deregulated during certain neoplastic conditions. The induction of both small RNAs are specific for tumor cells and might play a role in the pathogenesis of those cancer tissues under some circumstances.
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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.
