Alternative splice variants of rhomboid proteins: Comparative analysis of database entries for select model organisms and validation of functional potential
Bibliographic record
Abstract
<ns4:p> <ns4:bold>Background:</ns4:bold> 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 <ns4:italic>Arabidopsis</ns4:italic> showed that the number of rhomboid proteins working simultaneously can be further diversified by alternative splicing. This phenomenon was confirmed for the <ns4:italic>Arabidopsis</ns4:italic> plastid rhomboid proteins At1g25290 and At1g74130. Although alternative splicing was determined to be a significant mechanism for diversifying these two <ns4:italic>Arabidopsis</ns4:italic> plastid rhomboids, there has yet to be an assessment as to whether this mechanism extends to other rhomboids and to other species. </ns4:p> <ns4:p> <ns4:bold>Methods:</ns4:bold> We thus conducted a comparative analysis of select databases to determine if the alternative splicing mechanism observed for the two <ns4:italic>Arabidopsis</ns4:italic> plastid rhomboids was utilized in other species to expand the repertoire of rhomboid proteins. To help verify the <ns4:italic>in silico</ns4:italic> 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. </ns4:p> <ns4:p> <ns4:bold>Results:</ns4:bold> A comparison of database entries of six widely used eukaryotic experimental models (human, mouse, <ns4:italic>Arabidopsis</ns4:italic> , <ns4:italic>Drosophila</ns4:italic> , 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 <ns4:italic>Arabidopsis</ns4:italic> . Subsequent validation studies uncover evidence that the splice variants selected for testing displayed functionality in the different activity assays. </ns4:p> <ns4:p> <ns4:bold>Conclusions:</ns4:bold> 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. </ns4:p>
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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 | 0.001 |
| 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".