Programmable RNA <i>N</i><sup>1</sup>‐Methyladenosine Demethylation by a Cas13d‐Directed Demethylase
Bibliographic record
Abstract
Abstract N 1 ‐methyladenosine (m 1 A) is a prevalent and reversible RNA modification, which plays a crucial role in the regulation of RNA fate and gene expression. However, the lack of tools to precisely manipulate m 1 A sites in specific transcripts has hindered efforts to clarify the association between a specific m 1 A‐modified transcript and its phenotypic outcomes. Here we develop a CRISPR‐Cas13d‐based tool called re engineered m 1 A mo dification v alid er aser (termed “REMOVER”) for targeted m 1 A demethylation of a specific transcript. The catalytically inactive RfxCas13d (dCasRx) is fused to the m 1 A demethylase ALKBH3, and the dCasRx‐ALKBH3 fusion protein can mediate potent demethylation of m 1 A‐modified RNAs. We further find that REMOVER can specifically demethylate m 1 A of MALAT1 and PRUNE1 RNAs, thereby significantly increasing their stability. Our study establishes REMOVER as a tool for targeted RNA demethylation of specific m 1 A‐modified transcripts, which enables further elucidation of the relationship between m 1 A modification of specific transcripts and their phenotypic outcomes.
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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 | 0.000 |
| 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 | 0.000 |
| 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".