Biology subjects

Becskei, A.

Publications and source records attributed to Becskei, A..

3 recordsLinked to original sources

bioRxiv2026

Redistribution of codon-optimality effects: measurement strategy alters the division of labor between translation and mRNA decay

Codon optimality promotes efficient translation and, as recent research has shown, also extends mRNA lifetimes. However, how control is distributed between translation and mRNA degradation remains unclear. We show that this relative impact depends strongly on the measurement approach. Using fluorescent protein reporters can underestimate codon-optimality-dependent increases in translation efficiency. Conversely, analyses based on poly(A)-selected RNA overestimate the impact on translation, because stable transcripts undergoing poly(A) shortening are often inefficiently captured, leading to skewed protein-to-mRNA ratios. This technical bias is not offset by the marginal decline in ribosomal association observed as mRNAs age. Estimates based on total RNA measurements redistribute some of the control attributed to translation to mRNA stability, making the contributions comparable for mRNAs with shorter coding sequences. For longer mRNAs, codon optimality increasingly controls elongation speed, with a greater effect on translation efficiency than on degradation. These insights highlight the importance of measurement strategy for accurately quantifying the determinants of mRNA stability and protein synthesis.

biochemistry↗

bioRxiv2025

Heat shock induces silent ribosomes and reorganizes mRNA turnover

mRNAs associate with single or multiple ribosomes; these ribosomal assemblies -- monosomes and polysomes -- translate the mRNAs before degradation. The impact of heat stress on this mRNA turnover remains unclear. In heat-shocked yeast cells, the proportion of monosomes within the ribosomal assemblies rises without a corresponding increase in the number of mRNAs associated with them. As a result, most monosomes are devoid of mRNAs and silent, lacking translational initiation factors and proteins facilitating posttranslational folding. The accumulation of silent ribosomes generally reduces the rate of association of transcripts with the ribosomes. However, elevated temperatures enhance the ribosomal association of specific mRNAs, primarily those encoding heat-shock proteins, allowing them to balance their increased degradation rates. Additionally, reduced binding of the Xrn1 exonuclease to mRNAs diminishes the influence of codon optimality on mRNA stability. These mechanisms reorganize mRNA turnover to prioritize heat-shock protein synthesis over ribosome biogenesis.

genomics↗

bioRxiv2020

Gene families with stochastic exclusive gene choice underlie cell adhesion in mammalian cells

Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single cell RNA-seq data with a simple metric. Chromosomal segments and families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.

bioinformatics↗