La proteins couple use of sequence-specific and non-specific binding modes to engage RNA substrates
Bibliographic record
Abstract
La shuttles between the nucleus and cytoplasm where it binds nascent RNA polymerase III (pol III) transcripts and mRNAs, respectively. La protects the 3' end of pol III transcribed RNA precursors, such as pre-tRNAs, through the use of a well-characterized UUU-3'OH binding mode. La proteins are also RNA chaperones, and La-dependent RNA chaperone activity is hypothesized to promote pre-tRNA maturation and translation at cellular and viral internal ribosome entry sites via binding sites distinct from those used for UUU-3'OH recognition. Since the publication of La-UUU-3'OH co-crystal structures, biochemical and genetic experiments have expanded our understanding of how La proteins use UUU-3'OH-independent binding modes to make sequence-independent contacts that can increase affinity for ligands and promote RNA remodeling. Other recent work has also expanded our understanding of how La binds mRNAs through contacts to the poly(A) tail. In this review, we focus on advances in the study of La protein-RNA complex surfaces beyond the description of the La-UUU-3'OH binding mode. We highlight recent advances in the functions of expected canonical nucleic acid interaction surfaces, a heightened appreciation of disordered C-terminal regions, and the nature of sequence-independent RNA determinants in La-RNA target binding. We further discuss how these RNA binding modes may have relevance to the function of the La-related proteins.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 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".