Protein Synthesis and Degradation
Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response
Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153).Ribosome Reinitiation Directs Gene-specific Translation and Regulates the Integrated Stress Response
Background: eIF2α-P induced GADD34 and constitutively expressed CReP target PP1c to dephosphorylate eIF2α-P to dictate translation control of the ISR.Results: Differential expression of GADD34 and CReP is regulated by upstream ORF (uORF)-mediated ribosome reinitiation.Conclusion: uORFs regulate differential expression of GADD34 and CReP and are important for cell adaptation to stress.Significance: Regulation of eIF2α-P is central for protein homeostasis and cell viability.A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA
Background Regulatory +1 frameshifting in antizyme mRNA is central for polyamine level homeostasis. Results A nascent peptide stimulator of +1 frameshifting operates in Agaricomycete fungal antizyme mRNA. Conclusion Frameshifting can be stimulated by nascent peptide interactions with the ribosome's peptide exit tunnel in a polyamine-dependent manner. Significance Specific nascent peptide stimulators may be a more general and unappreciated feature of utilized ribosomal frameshifting.
