Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay
Abstract
Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the S. cerevisiae transcriptome undergoes -1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.
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BibTeX
@article{zhang2026ribosomes,
title = {{Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay}},
author = {Yujie Zhang and Lilit Nersisyan and Eliska Fürst and Ioannis Alexopoulos and Carlos Santolaria and Susanne Huch and Claudio Bassot and Elena Garre and Per Sunnerhagen and Ilaria Piazza and Vicent Pelechano},
journal = {Molecular Cell},
year = {2026},
month = oct,
doi = {10.1016/j.molcel.2025.04.022},
url = {https://hal.science/hal-05780594v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay
AU - Yujie Zhang
AU - Lilit Nersisyan
AU - Eliska Fürst
AU - Ioannis Alexopoulos
AU - Carlos Santolaria
AU - Susanne Huch
AU - Claudio Bassot
AU - Elena Garre
AU - Per Sunnerhagen
AU - Ilaria Piazza
AU - Vicent Pelechano
PY - 2026
DA - 2026/10/06
JO - Molecular Cell
DO - 10.1016/j.molcel.2025.04.022
UR - https://hal.science/hal-05780594v1
AB - Cells need to adapt their transcriptome to quickly match cellular needs in changing environments. mRNA abundance can be controlled by altering both its synthesis and decay. Here, we show how, in response to poor nutritional conditions, the bulk of the S. cerevisiae transcriptome undergoes -1 ribosome frameshifts and experiences an accelerated out-of-frame co-translational mRNA decay. Using RNA metabolic labeling, we demonstrate that in poor nutritional conditions, nonsense-mediated mRNA decay (NMD)-dependent degradation represents at least one-third of the total mRNA decay. We further characterize this mechanism and identify low codon optimality as a key factor for ribosomes to induce out-of-frame mRNA decay. Finally, we show that this phenomenon is conserved from bacteria to humans. Our work provides evidence for a direct regulatory feedback mechanism coupling protein demand with the control of mRNA abundance to limit cellular growth and broadens the functional landscape of mRNA quality control.
SN - 1097-2765
SN - 1097-4164
ER -