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Record W7132912350

The Role of the ORB2 RNA-binding Protein in Post-transcriptional Regulation

2023· dissertation· W7132912350 on OpenAlexaff
Timothy Low

Bibliographic record

VenueTSpace · 2023
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsAmgen (Canada)
Fundersnot available
KeywordsTranslation (biology)Translational regulationGeneMaternal to zygotic transitionEukaryotic translationRNAFunction (biology)Transcription preinitiation complexProtein domain
DOInot available

Abstract

fetched live from OpenAlex

RNA-binding proteins (RBPs) are key components of the post-transcriptional regulatory framework and can determine the translational fate of their RNA targets. A wide variety of post-transcriptional regulatory mechanisms are employed during the early Drosophila embryo and it has been established as a system well suited for the study of these mechanisms. In Drosophila, ORB2 is an RBP expressed in the early embryo. It has been shown to regulate translation of bound mRNAs, but relatively little is known about what RNAs it targets in early embryogenesis and the mechanisms by which it confers this regulation. In this thesis, I show that ORB2 associates with over 450 genes in the early embryo. Analysis of these genes shows that they are translationally repressed during the first two hours of development and are degraded during the maternal to zygotic transition (MZT). Using a dual luciferase assay, I show that ORB2 confers translational repression on a target mRNA and I map this repressive function to the C-terminal ZZ domain of the ORB2 protein. Next, I identify over 200 proteins which interact with ORB2 in the early embryo. This list of interactors includes protein components of the 43S preinitiation complex of translation initiation and components of the Cup repressive complex. I found that the ZZ domain is necessary for ORB2’s association with both complexes. Finally, I show that deletion of the ZZ domain of ORB2 causes major defects during the process of spermatogenesis. In these mutants, the localization of protein gradients to the apical tip of spermatid cysts is disrupted and the process of spermatid individualization fails to complete. These defects ultimately cause male sterility in these mutant flies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.010
GPT teacher head0.302
Teacher spread0.292 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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