Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay.

Zhang, Y.; Nersisyan, L.; Fuerst, E.; Alexopoulos, I.; Huch, S.; Bassot, C.; Garre, E.; Sunnerhagen, P.; Piazza, I.; Pelechano, V.

doi:10.1101/2024.03.12.584696

bioRxiv · 10.1101/2024.03.12.584696

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay.

Zhang, Y.·Nersisyan, L.·Fuerst, E.·Alexopoulos, I.·Huch, S.·Bassot, C.·Garre, E.·Sunnerhagen, P.·Piazza, I.·Pelechano, V.

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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 labelling, we demonstrate that in poor nutritional conditions, 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 expands the functional role of mRNA quality control.

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Zhang, Y., Nersisyan, L., Fuerst, E., Alexopoulos, I., Huch, S., Bassot, C., Garre, E., Sunnerhagen, P., Piazza, I., Pelechano, V.. 2024-03-12. Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay.. https://doi.org/10.1101/2024.03.12.584696

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