Identification of a link between splicing and endoplasmic reticulum proteostasis
Bibliographic record
Abstract
Abstract The role of general splicing in endoplasmic reticulum (ER)-proteostasis remains poorly understood. Here, we identify SNRPB, a component of the spliceosome, as a novel regulator of export from the ER. Mechanistically, SNRPB regulates the splicing of components of the ER export machinery, including Sec16A, a regulator of ER exit sites. Loss of function of SNRPB is causally linked to cerebro-costo-mandibular syndrome (CCMS), a genetic disease characterized by bone defects. We show that heterozygous deletion of SNRPB in mice resulted in intracellular accumulation of type-1 collagen as well as bone defects reminiscent of CCMS. Silencing SNRPB inhibited osteogenesis in vitro, which could be rescued by overexpression of Sec16A. This indicates that the role of SNRPB in osteogenesis is linked to its effects on ER export. Finally, we show that SNRPB is a target for the unfolded protein response (UPR), which supports a mechanistic link between the spliceosome and ER-proteostasis. Our work highlights SNRPB as a novel node in the proteostasis network, shedding light on CCMS pathophysiology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".