Ribosome-quality control antagonizes the activation of integrated-stress response on colliding ribosomes

Ribosome stalling occurring on aberrant mRNA activates quality control pathways to maintain proteostasis. Recently, ribosome stalling has also been linked to the activation of Gcn2 and the subsequent integrated-stress response (ISR). How the two processes are coordinated is not completely clear. Here we show that activation of ribosome-quality control by Hel2 suppresses that of Gcn2 in yeast. In the absence of Hel2, we observe a gene-expression signature indicative of ISR activation, suggesting that factor is used to suppress premature activation of Gcn2 in the absence of stress conditions. We further show that Hel2 and Gcn2 are activated by similar set of agents that cause ribosome stalling, with Hel2’s maximal activation occurring at lower frequency of stalling. Interestingly, inactivation of one pathway was found to result in the overactivation of the other, suggesting that both are activated by the same signal. Indeed, we provide evidence that suggests that, similar to Hel2, Gcn2 is activated by ribosome collisions. Collectively, our findings provide interesting details about how the multiple pathways that recognize stalled ribosomes coordinate to mount the appropriate response. Overall design: Libraries were constructed from RNA collected from various S. cerevisiae strains treated with or without methyl methanesulfonate (MMS).

Identifier
Source https://data.blue-cloud.org/search-details?step=~012FF8B94E49AC5BF827F2388216ED7E241474228AC
Metadata Access https://data.blue-cloud.org/api/collections/FF8B94E49AC5BF827F2388216ED7E241474228AC
Provenance
Instrument Illumina NovaSeq 6000; ILLUMINA
Publisher Blue-Cloud Data Discovery & Access service; ELIXIR-ENA
Publication Year 2024
OpenAccess true
Contact blue-cloud-support(at)maris.nl
Representation
Discipline Marine Science
Temporal Point 2020-05-20T00:00:00Z