A kinetic ruler controls mRNA poly(A) tail length
Bibliographic record
Abstract
Poly(A) tails of newly synthesized mRNAs have uniform lengths, arising through cooperation between the cleavage and polyadenylation complex (CPAC) and poly(A) binding proteins (PABPs). In the budding yeast Saccharomyces cerevisiae , the responsible PABP is the evolutionarily conserved CCCH zinc finger protein Nab2 that facilitates the biogenesis of ∼60 adenosine mRNA poly(A) tails. Here, we address the molecular basis for such length control. Reconstituting polyadenylation reactions during the formation of Nab2:poly(A) RNA ribonucleoprotein particles in vitro, we found that Nab2 dimerization directs polyadenylation termination. The Nab2 dimer is stable only on poly(A) tails that are >25 adenosines, explaining how Nab2 avoids prematurely terminating poly(A) synthesis. However, the mature tail length is not determined by the footprint of Nab2 on the RNA but rather by the kinetic competition between CPAC-mediated tail elongation and Nab2 RNA binding. Variations in Nab2 RNA binding rate can shift poly(A) tail lengths, but in cells such variations are buffered by autoregulation of Nab2 protein concentration. As a result, poly(A) tail length control operates through a “kinetic ruler” mechanism, whereby the concentration of Nab2 quantifies RNA length.
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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".