Selective inactivation of SIDER2 retroposon‐mediated mRNA decay contributes to stage‐ and species‐specific gene expression in <i>Leishmania</i>
Bibliographic record
Abstract
Despite their high genomic synteny, the Leishmania major and Leishmania infantum species exhibit extensive differences in mRNA expression patterns throughout the parasite's development. Yet, the underlying mechanisms for this species-specific differential gene expression are largely unknown. Here we report that Short Interspersed DEgenerated Retroposons of the SIDER2 subfamily, shown previously to promote rapid mRNA turnover, confer differential regulation of orthologous transcripts resulting in a stage- and species-specific gene expression. We demonstrate that SIDER2-mediated decay of two L. major transcripts encoding a hypothetical protein and an aminomethyltransferase to a similar extent in promastigote and amastigote developmental forms results in a constitutive low expression of the corresponding proteins. In contrast, their L. infantum orthologs are differentially expressed due to the selective inactivation of SIDER2 in intracellular amastigotes. Inactivation of the SIDER2 function blocks the SIDER2-mediated deadenylation-independent decay pathway, and stabilized transcripts are degraded by a slower, deadenylation-dependent mechanism. Sequence variations in SIDER2 retroposons between orthologous transcripts do not contribute to SIDER2 inactivation. Our data suggest that SIDER2 inactivation is 3'-untranslated region context-dependent and that involves possibly species- and stage-specific trans-acting factor(s). These findings further emphasize the important contribution of SIDER retroposons in the control of gene expression across the Leishmania genus.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".