We plan to study the principles of gene regulation in the nervous tissue, emphasizing RNA and its processing. In particular, the unusual poly(A)- mRNA which only in the brain has a high complexity and which is developmentally regulated will be analyzed via individual cDNA clones. A second line of experiments involves small brain-specific RNA with an initial stress on BCl RNA which has homologies to a repetitive Alu-like element, the identifier (ID) sequence. The outlined research will give insights into the structure, processing, developmental pattern and anatomical location of the poly(A)- RNAs. Indirectly, we will be able to deduce the protein coding sequences of these RNAs and test the presence of the polypeptides with antibodies to synthetic peptides as well as to gain from the protein structure some insight on their possible role in the nervous tissue. The genes of these RNAs will be studied with respect to common elements (e.g., common 3' processing sites or pomoter regions that regulate the timed levels of expression in development), the absence of introns, and possible relationships within gene families. Experiments on the second project, concerning brain specific small RNAs, will yield information on whether the non-ID part of the BCl RNA is heterologous, or consists mainly of A-residues. In that case we shall proceed directly to determine whether the RNA is part of a small cytoplasmic ribonucleoprotein complex (scRNP). If the remainder of the sequence is unique we shall also isolate the gene for the BCl RNA and examine its structure. Our studies might lead to future experiments focussing on the subcellular location and function of the particle. Furthermore, the possible role of BCl scRNP-antibodies in autoimmune diseases could be studied. In general, studying molecules which are specific to the brain might lead to the discovery of principles which are unique to that organ and which might give us insights in some of the mechanisms concerning memory, behavior, aging and mental diseases at the molecular level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH038819-02
Application #
3376944
Study Section
(BPNB)
Project Start
1985-05-01
Project End
1988-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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Kremerskothen, J; Zopf, D; Walter, P et al. (1998) Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain. Neurosci Lett 245:123-6
Cheng, J G; Tiedge, H; Brosius, J (1997) Expression of dendritic BC200 RNA, component of a 11.4S ribonucleoprotein particle, is conserved in humans and simians. Neurosci Lett 224:206-10
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Taylor, B A; Navin, A; Skryabin, B V et al. (1997) Localization of the mouse gene (Bc1) encoding neural BC1 RNA near the fibroblast growth factor 3 locus (Fgf3) on distal chromosome 7. Genomics 44:153-4
Shen, M R; Brosius, J; Deininger, P L (1997) BC1 RNA, the transcript from a master gene for ID element amplification, is able to prime its own reverse transcription. Nucleic Acids Res 25:1641-8
Tiedge, H; Brosius, J (1996) Translational machinery in dendrites of hippocampal neurons in culture. J Neurosci 16:7171-81
Cheng, J G; Tiedge, H; Brosius, J (1996) Identification and characterization of BC1 RNP particles. DNA Cell Biol 15:549-59
Martignetti, J A; Brosius, J (1995) BC1 RNA: transcriptional analysis of a neural cell-specific RNA polymerase III transcript. Mol Cell Biol 15:1642-50

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