Functional characterization of PAX5 gene circular products in B-cell development and function 4458
Bibliographic record
Abstract
Abstract Description PAX5 is crucial for B-lineage commitment and adaptive immunity. Recently, we identified a novel class of PAX5 products in B cells: circular RNAs (circRNAs). Given PAX5’s central role in B-cell biology, we hypothesized that PAX5 circRNAs (circPAX5) contribute to B-cell development and function. Using deep sequencing of B-cell lines and primary peripheral blood B-lymphocytes, we mapped 10 distinct circPAX5 isoforms comprising various exon and intron combinations from the PAX5 locus. Notably, the most abundant isoform, circPAX5 2-5, encompasses sequences exons 2 to 5. To explore circPAX5 signaling pathways, we isolated circPAX5 complexes from B-cell lines and characterized their co-interacting partners (miRNAs and proteins) via deep sequencing and mass spectrometry. Intriguingly, circPAX5 interacted with distinct signaling partners depending on the B-cell developmental stage. These findings suggest that circPAX5 plays stage-specific roles by engaging unique interaction networks across B-cell subtypes. To assess circPAX5’s phenotypic impact, we conditionally expressed circPAX5 in various B-cell lines. Similarly, we found that circPAX5 silencing altered cellular growth rates in a differentiation state- and subtype-dependent manner. Altogether, we present circPAX5 products as a new layer of signaling networks mediating B-cell biology. The functional elucidation of circPAX5 products may provide new insight to mechanisms supporting B-cell differentiation and immune development. Funding Sources Supported by NSERC-DDG-2020-00005 Topic Categories Hematopoiesis and Immune System Development (HEM)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".