Identification of Drosophila and Human 7-Methyl GMP-specific Nucleotidases
Bibliographic record
Abstract
Turnover of mRNA releases, in addition to the four regular nucleoside monophosphates, the methylated cap nucleotide in the form of 7-methylguanosine monophosphate (m7GMP) or diphosphate (m7GDP). The existence of pathways to eliminate the modified nucleotide seems likely, as its incorporation into nucleic acids is undesirable. Here we describe a novel 5′ nucleotidase from Drosophila that cleaves m7GMP to 7-methylguanosine and inorganic phosphate. The enzyme, encoded by the predicted gene CG3362, also efficiently dephosphorylates CMP, although with lower apparent affinity; UMP and the purine nucleotides are poor substrates. The enzyme is inhibited by elevated concentrations of AMP and also cleaves m7GDP to the nucleoside and two inorganic phosphates, albeit less efficiently. CG3362 has equivalent sequence similarity to two human enzymes, cytosolic nucleotidase III (cNIII) and the previously uncharacterized cytosolic nucleotidase III-like (cNIII-like). We show that cNIII-like also displays 5′ nucleotidase activity with a high affinity for m7GMP. CMP is a slightly better substrate but again with a higher Km. The activity of cNIII-like is stimulated by phosphate. In contrast to cNIII-like, cNIII and human cytosolic nucleotidase II do not accept m7GMP as a substrate. We suggest that the m7G-specific nucleotidases protect cells against undesired salvage of m7GMP and its incorporation into nucleic acids.Background: mRNA decay releases, in addition to the regular nucleotides, 7-methyl GMP derived from the 5′ cap.Results: We describe new members of the 5′ nucleotidase family degrading 7-methyl GMP to 7-methylguanosine and orthophosphate.Conclusion: Cells have mechanisms to prevent potential salvage of 7-methyl GMP.Significance: 7-Methyl GMP degradation may be important to prevent its incorporation into nucleic acids. Turnover of mRNA releases, in addition to the four regular nucleoside monophosphates, the methylated cap nucleotide in the form of 7-methylguanosine monophosphate (m7GMP) or diphosphate (m7GDP). The existence of pathways to eliminate the modified nucleotide seems likely, as its incorporation into nucleic acids is undesirable. Here we describe a novel 5′ nucleotidase from Drosophila that cleaves m7GMP to 7-methylguanosine and inorganic phosphate. The enzyme, encoded by the predicted gene CG3362, also efficiently dephosphorylates CMP, although with lower apparent affinity; UMP and the purine nucleotides are poor substrates. The enzyme is inhibited by elevated concentrations of AMP and also cleaves m7GDP to the nucleoside and two inorganic phosphates, albeit less efficiently. CG3362 has equivalent sequence similarity to two human enzymes, cytosolic nucleotidase III (cNIII) and the previously uncharacterized cytosolic nucleotidase III-like (cNIII-like). We show that cNIII-like also displays 5′ nucleotidase activity with a high affinity for m7GMP. CMP is a slightly better substrate but again with a higher Km. The activity of cNIII-like is stimulated by phosphate. In contrast to cNIII-like, cNIII and human cytosolic nucleotidase II do not accept m7GMP as a substrate. We suggest that the m7G-specific nucleotidases protect cells against undesired salvage of m7GMP and its incorporation into nucleic acids. Background: mRNA decay releases, in addition to the regular nucleotides, 7-methyl GMP derived from the 5′ cap. Results: We describe new members of the 5′ nucleotidase family degrading 7-methyl GMP to 7-methylguanosine and orthophosphate. Conclusion: Cells have mechanisms to prevent potential salvage of 7-methyl GMP. Significance: 7-Methyl GMP degradation may be important to prevent its incorporation into nucleic acids.
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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".