Global regulatory features of alternative splicing across tissues and within the nervous system of <i>C. elegans</i>
Bibliographic record
Abstract
Alternative splicing plays a major role in shaping tissue-specific transcriptomes. Among the broad tissue types present in metazoans, the central nervous system contains some of the highest levels of alternative splicing. Although many documented examples of splicing differences between broad tissue types exist, there remains much to be understood about the splicing factors and the cis sequence elements controlling tissue and neuron subtype-specific splicing patterns. By using translating ribosome affinity purification coupled with deep-sequencing (TRAP-seq) in Caenorhabditis elegans , we have obtained high coverage profiles of ribosome-associated mRNA for three broad tissue classes (nervous system, muscle, and intestine) and two neuronal subtypes (dopaminergic and serotonergic neurons). We have identified hundreds of splice junctions that exhibit distinct splicing patterns between tissue types or within the nervous system. Alternative splicing events differentially regulated between tissues are more often frame-preserving, are more highly conserved across Caenorhabditis species, and are enriched in specific cis regulatory motifs, when compared with other types of exons. By using this information, we have identified a likely mechanism of splicing repression by the RNA-binding protein UNC-75/CELF via interactions with cis elements that overlap a 5′ splice site. Alternatively spliced exons also overlap more frequently with intrinsically disordered peptide regions than constitutive exons. Moreover, regulated exons are often shorter than constitutive exons but are flanked by longer intron sequences. Among these tissue-regulated exons are several highly conserved microexons <27 nt in length. Collectively, our results indicate a rich layer of tissue-specific gene regulation at the level of alternative splicing in C. elegans that parallels the evolutionary forces and constraints observed across metazoa.
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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) | 0.000 | 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".