Histone mRNA concentrations are regulated in parallel with DNA synthesis. There are two classes of histone mRNA; the major class which is regulated and codes for the replication histone variants, and a minor class, which is constitutively expressed by codes for replacement histone variants. The histone mRNA levels are regulated during the cell cycle and the signals which regulate DNA and histone synthesis may be related. Three major questions will be addressed: 1. What are the nucleic acid sequences involved in regulation of histone mRNA levels. These include DNA sequences involved in regulation of transcription and mRNA sequences involved in regulation of mRNA half-life. In particular, what are the differences in gene structure between the replication and replacement histone variants which differ in their regulation. We will answer this question by constructing variant genes, introducing them into cells and monitoring their regulatory behavior. In particular we will construct hybrid genes containing different portions of replication and replacement variant histones to see which portions are important in regulation. 2. What is the signal which regulates histone mRNA levels? The levels of histone mRNA are regulated by agents which alter deoxynucleotide metabolism. The hypothesis that an unusual nucleotide regulates histone mRNA levels will be tested. Changes in intracellular nucleotides which occur concominantly with alterations in histone mRNA levels will be analyzed. A cell-free system which may be used to assay for this signal will be developed. 3. Why is one cluster of histone genes on chromosome 3 expressed in 5 to 10 times the amount of the histone genes on chromosome 13? Genes will be constructed to test for the possibility of enhancer sequences on the histone genes on chromosome 3.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM029832-09
Application #
3277516
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1982-07-01
Project End
1990-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Florida State University
Department
Type
Schools of Arts and Sciences
DUNS #
020520466
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
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Skrajna, Aleksandra; Yang, Xiao-Cui; Bucholc, Katarzyna et al. (2017) U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem-loop binding protein. RNA 23:938-951
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Lackey, Patrick E; Welch, Joshua D; Marzluff, William F (2016) TUT7 catalyzes the uridylation of the 3' end for rapid degradation of histone mRNA. RNA 22:1673-1688
Skrajna, Aleksandra; Yang, Xiao-Cui; Tarnowski, Krzysztof et al. (2016) Mapping the Interaction Network of Key Proteins Involved in Histone mRNA Generation: A Hydrogen/Deuterium Exchange Study. J Mol Biol 428:1180-1196
Djakbarova, Umidahan; Marzluff, William F; Köseo?lu, M Murat (2016) DDB1 and CUL4 associated factor 11 (DCAF11) mediates degradation of Stem-loop binding protein at the end of S phase. Cell Cycle 15:1986-96
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