M-Motif, a potential non-conventional NLS in YAP/TAZ and other cellular and viral proteins that inhibits classic protein import
Bibliographic record
Abstract
Multiple mechanisms were proposed to mediate the nuclear import of TAZ/YAP, transcriptional co-activators regulating organ growth and regeneration. Our earlier observations showed that TAZ/YAP harbor a C-terminal, unconventional nuclear localization signal (NLS). Here, we show that this sequence, necessary and sufficient for basal, ATP-independent nuclear import, contains an indispensable central methionine flanked by negatively charged residues. Based on these features, we define the M-motif and propose that it is a new class of NLS, also present and import-competent in other cellular (STAT1 and cyclin B1) and viral (ORF6 of SARS-CoV2, VSV-M) proteins. Accordingly, ORF6 SARS-Cov2 competitively inhibits TAZ/YAP uptake, while TAZ abrogates STAT1 import. Similar to viral M-motif proteins, TAZ binds RAE1 and inhibits classic nuclear protein import, including that of antiviral factors (IRF3 and NF-κB). However, RAE1 is dispensable for TAZ import itself. Thus, the TAZ/YAP NLS has a dual function: it mediates unconventional nuclear import and inhibits classic import, contributing to the suppression of antiviral responses.
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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".