Mistranslation suppresses mistranscription in eukaryotes

Area of Science:

• Molecular Biology
• Genetics
• Evolutionary Biology

Background:

• Phenotypic mutations arise from non-heritable sequence changes like mistranscription and mistranslation.
• The interplay between mistranscription and mistranslation is not well understood despite their potential impact.

Purpose of the Study:

• To investigate the relationship between mistranscription and mistranslation rates across the genome.
• To explore the underlying mechanisms, such as epistasis, that may govern this interaction.

Main Methods:

• Genome-wide analysis using Circ-Seq and mass spectrometry in five model organisms.
• Systematic experimental measurements to confirm epistasis.
• In silico evolutionary simulations.
• Empirical genomic analyses of gene expression and error purging.

Main Results:

• Genes with high mistranslation rates exhibit lower mistranscription rates.
• Negative epistasis between mistranscription and mistranslation was experimentally confirmed.
• Evolutionary simulations indicated selection against mistranscription in highly mistranslated genes due to epistasis.
• Genes with high mistranslation efficiently purge nonsynonymous mistranscriptions, and highly translated transcripts have fewer mistranscriptions.

Conclusions:

• An unrecognized negative interaction exists between mistranscription and mistranslation.
• This interaction impacts evolutionary dynamics and gene expression regulation.
• The findings highlight a novel layer of molecular error management within cells.