O‐GlcNAc occurs cotranslationally to stabilize nascent polypeptides
Bibliographic record
Abstract
Nucleocytoplasmic glycosylation of proteins with O‐linked N‐acetylglucosamine residues (O‐GlcNAc) is mediated by the glycosyltransferase O‐GlcNAc transferase (OGT). O‐GlcNAc is recognized as a common post‐translational modification and is found on hundreds of proteins within all metazoans studied to date. O‐GlcNAc has emerged as a regulator of diverse cellular processes ranging from gene expression through to circadian rhythm. Notably, impairments in cellular O‐GlcNAcylation have been found to lead to decreases in the levels of various proteins and this is one mechanism by which O‐GlcNAc seems to exert its varied physiological effects. Here we use a chemical biology approach in combination with biochemical fractionation to show that O‐GlcNAcylation also occurs on polypeptides that are emerging from the ribosome. Using both chemical and genetic blockade of OGT we show that this cotranslational O‐GlcNAcylation protects nascent polypeptide chains from premature degradation by decreasing their cotranslational ubiquitylation. Given that hundreds of proteins are O‐GlcNAcylated within cells, our findings suggest that cotranslational O‐GlcNAcylation may be a phenomenon regulating proteostasis of an array of nucleocytoplasmic proteins. We describe our recent findings and discuss the similarities between cotranslational O‐GlcNAcylation and the roles played by cotranslational N‐glycosylation occurring within the secretory pathway. Support or Funding Information Financial support through a Discovery Grant (Grant number: RGPIN/298406‐2010) the Natural Sciences and Engineering Research (NSERC) and the Canadian Institutes of Health Research (CIHR) (Grant number: MOP‐102756) is gratefully acknowledged. Y.Z. thanks the CIHR for support through a postdoctoral fellowship. D.J.V. acknowledges the kind support of the Canada Research Chairs program for a Tier I Canada Research Chair in Chemical Glycobiology and NSERC for support as an E.W.R. Steacie Memorial Fellow.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".