Translation affects mRNA stability in a codon-dependent manner in human cells.

Area of Science:

• Molecular Biology
• Gene Regulation
• Post-transcriptional Modification

Background:

• mRNA translation decodes nucleotide sequences into amino acids.
• Codon composition has been linked to mRNA stability in model organisms, but universality is unclear.
• The precise role of codons in human mRNA stability requires further investigation.

Purpose of the Study:

• To identify specific codons associated with mRNA stability or instability in human cells.
• To determine if regulatory information for mRNA stability is encoded in codons or nucleotides.
• To elucidate the role of translation and tRNA availability in codon-mediated mRNA stability.

Main Methods:

• Utilized three independent methods to measure exogenous and endogenous mRNA decay in human cells.
• Analyzed the correlation between codon composition and mRNA decay rates.
• Investigated the relationship between tRNA levels, charged/total tRNA ratios, and mRNA stability.
• Assessed the role of the poly(A)-tail and ribosome loading in codon-mediated effects.

Main Results:

• Defined specific codons that confer stability or instability to mRNAs in human cells.
• Demonstrated that codons, not nucleotides, contain the regulatory information for mRNA stability.
• Found stabilizing codons correlate with higher tRNA levels and charged/total tRNA ratios.
• Observed that shorter poly(A)-tails are associated with destabilizing codons, but the poly(A)-tail is not essential for this mechanism.
• Confirmed that translation is required, and ribosome loading modulates codon-mediated effects.

Conclusions:

• Codon composition is a critical determinant of mRNA stability in human cells.
• This codon-dependent mRNA stability mechanism is conserved and functions via translation.
• The findings reveal a novel layer of gene expression regulation at the post-transcriptional level.