Stress induces DCP2 translation via a stalling-dependent mechanism

Authors

Roiuk, M., Neff, M., Vatovec, T., Papazian, A., Helms, V., Teleman, A. A.

Abstract

The integrated stress response (ISR) globally suppresses protein synthesis while selectively permitting translation of a small subset of stress-responsive mRNAs, many of which contain upstream or overlapping open reading frames (uORFs/oORFs). Although translational induction of transcripts such as ATF4 has classically been attributed to delayed re-initiation caused by reduced ternary complex availability, the mechanisms by which uORFs and oORFs allow ISR-selective translation remain incompletely understood. Here, using ribosome profiling during early ISR activation combined with reporter assays, we identify DCP2, encoding a major mRNA decapping enzyme, as a previously unrecognized ISR-induced transcript. We show that translational induction of DCP2 depends on an overlapping ORF whose conserved 3' region, corresponding to a ribosome pausing site, acts as a potent inhibitory element. Both the DCP2 oORF and main ORF increase in translation during stress, indicating that stress relieves repression by this inhibitory element. This reveals a mode of ISR-dependent gene regulation in which inhibition by a nascent peptide or stalling element embedded either in a uORF or an oORF is relieved upon stress to induce translation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 27 Aug 2026.

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