Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2
Bibliographic record
Abstract
The gene Mest (also known as Peg1) is regulated by genomic imprinting in the mouse and only the paternal allele is active for transcription. MEST is similarly imprinted in humans, where it is a candidate for the growth retardation Silver-Russell syndrome. The MEST protein belongs to an ancient family of hydrolases but its function is still unknown. It is highly conserved in vertebrates although imprinted expression is only observed in marsupials and eutherians, thus a recent evolutionary event. Here we describe the identification of new imprinted RNA products at the Mest locus, longer variants of the RNA, called MestXL, transcribed >10 kb into the downstream antisense gene Copg2. During development MestXL is produced exclusively in the developing central nervous system (CNS) by alternative polyadenylation. Copg2 is biallelically expressed in the embryo except in MestXL-expressing tissues, where we observed preferential expression from the maternal allele. To analyze the function of the MestXL transcripts in Copg2 regulation, we studied the effects of a targeted allele at Mest introducing a truncation in the mRNA. We show that both the formation of the MestXL isoforms and the allelic bias at Copg2 are lost in the CNS of mutants embryos. Our results propose a new mechanism to regulate allelic usage in the mammalian genome, via tissue-specific alternative polyadenylation and transcriptional interference in sense-antisense pairs at imprinted loci.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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 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".