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Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in the cell and is a major control point for modulating gene expression. In yeast and other model organisms, codon identity is a powerful determinant of transcript stability, contributing broadly to impact half-lives. General principles governing mRNA stability are poorly understood in mammalian systems. Importantly, however, the degradation machinery is highly conserved, thus it seems logical that mammalian transcript half-lives would also be strongly influenced by coding determinants. Herein we characterize the contribution of coding sequence towards mRNA decay in human and Chinese Hamster Ovary cells. In agreement with previous studies, we observed that synonymous codon usage impacts mRNA stability in mammalian cells. Surprisingly, however, we also observe that the amino acid content of a gene is an additional determinant correlating with transcript stability. The impact of codon and amino acid identity on mRNA decay appears to be associated with underlying tRNA and intracellular amino acid concentrations. Accordingly, genes of similar physiological function appear to coordinate their mRNA stabilities in part through codon and amino acid content. Together, these results raise the possibility that intracellular tRNA and amino acid levels interplay to mediate coupling between translational elongation and mRNA degradation rate in mammals.
This article was published in the following journal.
Name: PloS one
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An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.
The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.
An APOBEC deaminase catalytic subunit of the apolipoprotein B (APOB) MESSENGER RNA (mRNA) editing enzyme complex that is involved in post-transcriptional editing of a CAA codon for GLYCINE to a UAA STOP CODON in the ApoB mRNA. It also functions in CGA (ARGININE) to UGA STOP CODON editing of NEUROFIBROMIN 1 mRNA and EPIGENETIC PROCESSES.
A process of GENETIC TRANSLATION whereby the last amino acid is added to a lengthening polypeptide. This termination is signaled from the MESSENGER RNA, by one of three termination codons (CODON, TERMINATOR) that immediately follows the last amino acid-specifying CODON.
An mRNA metabolic process that distinguishes a normal STOP CODON from a premature stop codon (NONSENSE CODON) and facilitates rapid degradation of aberrant mRNAs containing premature stop codons.
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Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...