Nova regulation of alternative splicing in the CNS [microform]
- Bib ID:
- 3284374
- Format:
- Book and Microform
- Author:
- Dredge, Belinda Kate
- Description:
- 179 p.
- ISBN:
- 0493686207
- Summary:
-
Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a disorder associated with gynecologic cancer and CNS motor dysfunction, is a neuron-specific nuclear RNA binding protein. The work presented here confirms that Nova-1 acts as a regulator of alternative splicing in vivo. In addition to the known target of Nova-dependent splicing regulation, exon 3A of glycine receptor a2 subunit (GlyRa2), two new targets are identified, which are the alternative exon, E9 in the inhibitory neurotransmitter receptor subunit, GABAARG2, and the alternatively spliced exon H in Nova-1's own message. Nova acts to enhance alternative exon inclusion in GlyRa2 and GABAARG2 mRNAs and to repress alternative exon usage in its own message, thus acting as a dual function splicing regulator.
Sequence elements necessary and sufficient for Nova-dependent splicing regulation of these two new targets were elucidated, and a model is presented whereby Nova differentially regulates exon inclusion in a manner dependent on the location of the Nova binding site within the pre-mRNA. Also, Nova proteins localize to distinct subnuclear foci, but fail to co-localize with a number of known proteins that occupy sub-nuclear structural domains. Unlike nuclear speckles, which contain a number of other splicing factors, Nova foci are disrupted by treatment of the cells with actinomycin-D, consistent with the hypothesis that the formation and maintenance of Nova foci is an active process that is transcription dependent. Finally, differential gene expression screens were undertaken, leading to the identification of a number of additional potential targets of Nova regulation.
- Notes:
-
- (UnM)AAI3053193
- Source: Dissertation Abstracts International, Volume: 63-05, Section: B, page: 2227.
- Chair: Nathaniel Heintz.
- Thesis (Ph.D.)--The Rockefeller University, 2002.
- Reproduction:
- Microfiche. Ann Arbor, Mich.: University Microfilms International.
- Subject:
- Biology, Neuroscience
- Other authors/contributors:
- The Rockefeller University
- Copyright:
-
In Copyright
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Copyright status was determined using the following information:
- Material type:
- Literary Dramatic Musical
- Published status:
- Unpublished
- Creation date:
- 2002
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