Control of Translation at the Initiation Phase During Glucose Starvation in Yeast

Abstract

Glucose is one of the most important sources of carbon across all life. Glucose starvation is a key stress relevant to all eukaryotic cells. Glucose starvation responses have important implications in diseases, such as diabetes and cancer. In yeast, glucose starvation causes rapid and dramatic effects on the synthesis of proteins (mRNA translation). Response to glucose deficiency targets the initiation phase of translation by different mechanisms and with diverse dynamics. Concomitantly, translationally repressed mRNAs and components of the protein synthesis machinery may enter a variety of cytoplasmic foci, which also form with variable kinetics and may store or degrade mRNA. Much progress has been made in understanding these processes in the last decade, including with the use of high-throughput/omics methods of RNA and RNA:protein detection. This review dissects the current knowledge of yeast reactions to glucose starvation systematized by the stage of translation initiation, with the focus on rapid responses. We provide parallels to mechanisms found in higher eukaryotes, such as metazoans, for the most critical responses, and point out major remaining gaps in knowledge and possible future directions of research on translational responses to glucose starvation.

Integrated multi-omics reveals common properties underlying stress granule and P-body formation

“…Interestingly, whilst eIF4G1 and eIF4G2 targets in unstressed cells tend to localise to pre-PBs, pre-SGs, PBs and SGs, their targets (along with those of eIF4E) after glucose depletion do not and are under-enriched. This result highlights the importance of eIF4G in the dramatic translational reorganisation that occurs after glucose depletion and is in keeping with the rapid alterations in eIF4G interaction with eIF4A and eIF3 coincident with the translation inhibition (Castelli et al, 2011, Janapala et al, 2019.…”

“…Any role for Ded1p and eIF4A could be either direct via effects on the RNA structure or indirect via effects on mRNA translation. Indeed, both eIF4A and Ded1p may play roles in the rapid inhibition of translation that occurs after glucose depletion (Castelli, Lui et al, 2011, Janapala, Preiss et al, 2019.…”

Stress-Induced Translation Inhibition through Rapid Displacement of Scanning Initiation Factors

“…Translation initiation is generally the rate-limiting step in protein synthesis and a frequent target of regulation, including during stress (reviewed in Crawford and Pavitt, 2019 ; Dever et al., 2016 ; and Janapala et al., 2019 ). The initiation process begins with assembly of the 43S preinitiation complex (PIC), composed of the 40S subunit plus eukaryotic initiation factor 1 (eIF1), eIF1A, eIF3, eIF5, and eIF2:GTP in complex with the initiator tRNA ( Hinnebusch, 2017 ).…”

Stress-induced translation inhibition through rapid displacement of scanning initiation factors

“…Translation initiation is generally the rate-limiting step in protein synthesis, and a frequent target of regulation, including during stress; reviewed in (Crawford and Pavitt, 2019;Dever et al, 2016;Janapala et al, 2019). The initiation process begins with assembly of the 43S pre-initiation complex (PIC), comprised of the 40S subunit plus eIF1, eIF1A, eIF3, eIF5, and eIF2:GTP in complex with the initiator tRNA (Hinnebusch, 2017).…”