Ribonuclease activity undermines immune sensing of naked extracellular RNA
Bibliographic record
Abstract
Cell membranes are thought of as barriers to extracellular RNA (exRNA) uptake. While naked exRNAs can be spontaneously internalized by certain cells, functional cytosolic delivery has been rarely observed. Here, we show that extracellular ribonucleases (RNases)-primarily from cell culture supplements-have obscured the study of exRNA functionality. When ribonuclease inhibitor (RI) is added to cell cultures, naked exRNAs can trigger pro-inflammatory responses in dendritic cells and macrophages, largely via endosomal Toll-like receptors (TLRs). Moreover, naked exRNAs can escape endosomes, engaging cytosolic RNA sensors. In addition, naked extracellular mRNAs can be spontaneously internalized and translated by various cell types in an RI-dependent manner. In vivo, RI co-injection amplifies naked-RNA-induced activation of splenic lymphocytes and myeloid leukocytes. Furthermore, naked RNA is inherently pro-inflammatory in RNase-poor compartments like the peritoneal cavity. These findings demonstrate that naked RNA is bioactive without requiring vesicular encapsulation, making a case for nonvesicular-exRNA-mediated intercellular communication.
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".