Involvement of the 5'-leader sequence in coupling the stability of a human H3 histone mRNA with DNA replication

Journal Article · Sat Feb 01 04:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.4.981· OSTI ID:6155997

Morris, T; Marashi, F; Weber, L; Hickey, E; Greenspan, D; Bonner, J; Stein, J; Stein, G

Two lines of evidence derived from fusion gene constructs indicate that sequences residing in the 5'-nontranslated region of a cell cycle-dependent human H3 histone mRNA are involved in the selective destabilization that occurs when DNA synthesis is terminated. The experimental approach was to construct chimeric genes in which fragments of the mRNA coding regions of the H3 histone gene were fused with fragments of genes not expressed in a cell cycle-dependent manner. After transfection in HeLa S3 cells with the recombinant plasmids, levels of fusion mRNAs were determined by S1 nuclease analysis prior to and following DNA synthesis inhibition. When the first 20 nucleotides of an H3 histone mRNA leader were replaced with 89 nucleotides of the leader from a Drosophila heat-shock (hsp70) mRNA, the fusion transcript remained stable during inhibition of DNA synthesis, in contrast to the rapid destabilization of the endogenous histone mRNA in these cells. In a reciprocal experiment, a histone-globin fusion gene was constructed that produced a transcript with the initial 20 nucleotides of the H3 histone mRNA substituted for the human US -globin mRNA leader. In HeLa cells treated with inhibitors of DNA synthesis and/or protein synthesis, cellular levels of this histone-globin fusion mRNA appeared to be regulated in a manner similar to endogenous histone mRNA levels. These results suggest that the first 20 nucleotides of the leader are sufficient to couple histone mRNA stability with DNA replication.

• Research Organization: Univ. of Florida, Gainesville
• OSTI ID: 6155997
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 83:4; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ARTHROPODS
BACTERIA
BIODEGRADATION
CELL CONSTITUENTS
CELL CYCLE
CHEMICAL REACTIONS
DECOMPOSITION
DIPTERA
DNA REPLICATION
DNA SEQUENCING
DROSOPHILA
ESCHERICHIA COLI
FLIES
FRUIT FLIES
GENE REGULATION
GLOBIN
HELA CELLS
HISTONES
HYBRIDIZATION
INSECTS
INVERTEBRATES
MAMMALS
MAN
MESSENGER-RNA
MICROORGANISMS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PLASMIDS
PRIMATES
PROTEINS
RNA
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES