Alternative splice variants of rhomboid proteins: Comparative analysis of database entries for select model organisms and validation of functional potential
Bibliographic record
Abstract
Background: Rhomboid serine proteases are present across many species and are often encoded in each species by more than one predicted gene. Based on protein sequence comparisons, rhomboids can be differentiated into groups - secretases, presenilin-like associated rhomboid-like (PARL) proteases, iRhoms, and “inactive” rhomboid proteins. Although these rhomboid groups are distinct, the different types can operate simultaneously. Studies in Arabidopsis showed that the number of rhomboid proteins working simultaneously can be further diversified by alternative splicing. This phenomenon was confirmed for the Arabidopsis plastid rhomboid proteins At1g25290 and At1g74130. Although alternative splicing was determined to be a significant mechanism for diversifying these two Arabidopsis plastid rhomboids, there has yet to be an assessment as to whether this mechanism extends to other rhomboids and to other species. Methods: We thus conducted a comparative analysis of select databases to determine if the alternative splicing mechanism observed for the two Arabidopsis plastid rhomboids was utilized in other species to expand the repertoire of rhomboid proteins. To help verify the in silico observations, select splice variants from different groups were tested for activity using transgenic- and additive-based assays. These assays aimed to uncover evidence that the selected splice variants display capacities to influence processes like antimicrobial sensitivity. Results: A comparison of database entries of six widely used eukaryotic experimental models (human, mouse, Arabidopsis , Drosophila , nematode, and yeast) revealed robust usage of alternative splicing to diversify rhomboid protein structure across the various motifs or regions, especially in human, mouse and Arabidopsis . Subsequent validation studies uncover evidence that the splice variants selected for testing displayed functionality in the different activity assays. Conclusions: The combined results support the hypothesis that alternative splicing is likely used to diversify and expand rhomboid protein functionality, and this potentially occurred across the various motifs or regions of the protein.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".