The Role of Cytoplasmic Poly(A)-Binding Protein in Modulating the Mammalian Transcriptome
Bibliographic record
Abstract
Gene expression is a tightly regulated process fundamental to cellular function, identity, and adaptation.Among the key regulators of post-transcriptional gene expression, cytoplasmic poly(A)-binding proteins (PABPCs) play a crucial role in controlling mRNA stability, translation efficiency, and decay.This thesis investigates the context-dependent functions of PABPCs in mammalian cells, with a particular focus on their interactions with translation factors, mRNA decay machinery, and stress response pathways.I examine how PABPCs influence translation efficiency under different cellular conditions, challenging the conventional closed-loop model of translation, which posits that PABPC bridges the 5' cap and 3' poly(A) tail to enhance translation initiation.Recent findings indicate that not all mRNAs adopt a closed-loop conformation, suggesting alternative mechanisms for ribosome recruitment.Additionally, this work explores the role of PABPCs in stress granule dynamics, particularly in relation to neurodegenerative diseases.Furthermore, this thesis highlights the interplay between PABPCs and viral infections, where certain viruses manipulate PABPC interactions to hijack host translation machinery.By integrating insights from molecular biology, structural biochemistry, and cellular imaging studies, this research provides a comprehensive overview of PABPC function and its broader implications for gene expression regulation, disease mechanisms, and potential therapeutic interventions.These findings emphasize that PABPC activity is highly adaptable, influenced by cell type, environmental stress, and pathological conditions.Understanding the diverse roles of PABPCs opens new avenues for targeted therapies in cancer, viral infections, and neurodegenerative disorders.Résumé (French) L'expression génique est un processus finement régulé, fondamental pour la fonction, l'identité et l'adaptation cellulaires.Parmi les régulateurs clés de l'expression génique posttranscriptionnelle, les protéines de liaison à la queue poly(A) cytoplasmiques (PABPCs) jouent un rôle essentiel dans le contrôle de la stabilité des ARNm, de l'efficacité de la traduction et de leur dégradation.Cette thèse explore les fonctions contextuelles des PABPCs dans les cellules de mammifères, en mettant l'accent sur leurs interactions avec les facteurs de traduction, les voies de dégradation des ARNm et les réponses au stress cellulaire.J'analyse comment les PABPCs influencent l'efficacité de la traduction selon les conditions cellulaires, en remettant en question le modèle de boucle fermée qui propose que les PABPCs
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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 | 0.001 | 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".