NoncanonicalTransmission of Biological Information and Master-regulation of Signaling by the Zinc Finger Proteins MSTR-1 and MSTR-2
Bibliographic record
Abstract
Heritable information is encoded in nucleic acids and transmitted by an immortal germ lineage. Failure of germ cells to clear DNA damage or maintain small RNA expression leads to progressive sterility (germline mortality) over multiple generations due to accumulation of defects such as telomere erosion or transposon mobilization. Here, I show that solid-phase protein amyloids, which I propose to term ‘fluorosomes’ for their intrinsic fluorescence, are inherited transgenerationally and transmit the epigenetic information required for proper germ cell sex determination and germline immortality. I identify two genes, which I term multigenerational sterility and temperature regulated (F22D6.2/mstr-1 and F56F3.4/mstr-2), that when ablated lead to transgenerational accumulation of these fluorosomes and progressive transformation of germ cells from spermatogenic to oogenic fates. Among its key targets, MSTR-1 restricts expression of the sex determinant GLD-1 from spermatogenic cells, whereas in mstr mutants GLD-1 protein but not mRNA accumulates ectopically over several generations, transforming sperm-fated germ cells to oocytes. I further chronicle the discovery of these genes and the work that led to them, from investigation of their roles in cell signaling to the serendipitous discovery of their roles in germline function. Briefly, I show that insulin-like growth factor receptor DAF-2 signaling regulates DAF-16/FOXO dependent and independent networks to modulate LET-60/Ras function in the soma. The FOXO independent mechanism relies on the transcription factor PQM1, which is regulated by the SGK-1 kinase. The transcriptional target of PQM-1, mstr-1, regulates diverse cell signalling pathways important for multiple developmental processes, including vulval cell fate specification, germline proliferation, and longevity. Overall, my work reveals a post-transcriptional transgenerational epigenetic mechanism of trait transmission and demonstrates that germline immortality can be lost independently of DNA or RNA maintenance.
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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 | 0.001 |
| 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".