LINE-1: an emerging initiator of cGAS-STING signalling and inflammation that is dysregulated in disease
Bibliographic record
Abstract
The cGAS-STING (cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)) axis integrates DNA damage and cellular stress with type I interferon (IFN) signalling to facilitate transcriptional changes underlying inflammatory stress responses. The cGAS-STING pathway responds to cytosolic DNA in the form of double-stranded DNA, micronuclei, and long interspersed nuclear element 1 (L1) retroelements. L1 retroelements are a class of self-propagating non-long terminal repeat transposons that have remained highly active in mammalian genomes. L1 retroelements are emerging as important inducers of cGAS-STING and IFN signalling, which are often dysregulated in several diseases, including cancer. A key repressor of cGAS-STING and L1 activity is the exonuclease three prime repair exonuclease 1 (TREX1), and loss of TREX1 promotes the accumulation of L1. In addition, L1 dysregulation is a common theme among diseases with chronic induction of type I IFN signalling through cGAS-STING, such as Aicardi-Goutières syndrome, Fanconi anemia, and dermatomyositis. Although TREX1 is highly conserved in tetrapod species, other suppressor proteins exist that inhibit L1 retrotransposition. These suppressor genes when mutated are often associated with diseases characterized by unchecked inflammation that is associated with high cGAS-STING activity and elevated levels of L1 expression. In this review, we discuss these interconnected pathways of L1 suppression and their role in the regulation of cGAS-STING and inflammation in disease.
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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) | 0.001 | 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 | 0.001 | 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".