Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of <i>oskar</i> translation
Bibliographic record
Abstract
Abstract Makorins are evolutionary conserved proteins that contain C 3 H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar . We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds osk 3’ UTR in a region adjacent to A-rich sequences. This binding site overlaps with Bruno1 (Bru1) responsive elements (BREs), which regulate osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation by displacing Bru1 from its 3’ UTR. Author Summary To ensure accurate development of the Drosophila embryo, proteins and mRNAs are positioned at specific sites within the embryo. Many of these proteins and mRNAs are produced and localized during the development of the egg in the mother. One protein essential for this process that has been heavily studied is Oskar (Osk), which is positioned at the posterior pole. During the localization of osk mRNA, its translation is repressed by the RNA-binding protein Bruno1 (Bru1), ensuring that Osk protein is not present outside of the posterior where it is harmful. At the posterior pole, osk mRNA is activated through mechanisms that are not yet understood. In this work, we show that the conserved protein Makorin 1 (Mkrn1) is a novel factor involved in the translational activation of osk . Mkrn1 binds specifically to osk mRNA in a region that overlaps with the binding site of Bru1, thus alleviating the association of Bru1 with osk . Moreover, Mkrn1 is stabilized by poly(A) binding protein, a translational activator that binds osk mRNA in close proximity to Mkrn1. Our work thus helps to answer a long-standing question in the field, providing insight about the function of Mkrn1 and more generally into embryonic patterning in animals.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".