Leader length and secondary structure modulate mRNA function under conditions of stress
Simina virus 40-based plasmids that direct the synthesis of preproinsulin in cultured monkey cells were used to study the effects of mRNA structure on translational efficiency. Lengthening the leader sequence enhanced translation in this system. The enhancement was most obvious when an unstructured sequence (two, four, or eight copies of the oligonculeotide AGCTAAGTAAGTAAGTA) was inserted upstream from a region of deliberate secondary structure; the degree of enhancement was proportional to the number of copies of the inserted oligonucleotide. Lengthening the leader sequence on the 3' side of a stem-and-loop structure, in contrast, did not offset the potentially inhibitory effect of the hairpin structure. Both the facilitating effect of length and the inhibitory effect of secondary structure were demonstrated most easily under conditions of mRNA competition, which was brought about by an abrupt shift in the tonicity of the culture medium. These experiments suggest a simple structural basis for the long-recognized differential response of viral and cellular mRNAs to hypertonic stress. The fact that the translatability of structure-prone mRNAs varies with changes in the environment may also have general implications for gene expression in eucaryotic cells.
- Research Organization:
- Dept. of Biological Sciences, Univ. of Pittsburgh, Pittsburgh, PA (US)
- OSTI ID:
- 6465770
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 8:7
- Country of Publication:
- United States
- Language:
- English
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GENE OPERONS
DNA SEQUENCING
MOLECULAR BIOLOGY
INSULIN
RNA PROCESSING
CELL CULTURES
EXPERIMENTAL DATA
GENES
MESSENGER-RNA
MODULATION
MONKEYS
OLIGONUCLEOTIDES
PHENOTYPE
PLASMIDS
SIMIAN VIRUS
STRESS ANALYSIS
VARIATIONS
ANIMALS
CELL CONSTITUENTS
DATA
HORMONES
INFORMATION
MAMMALS
MICROORGANISMS
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
PARASITES
PEPTIDE HORMONES
PRIMATES
RNA
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
VIRUSES
550200* - Biochemistry