Flipons, Noncoding Transcripts and Retroelements: A Universal Host Defense.
- 1Discovery, InsideOutBio, Charlestown, MA 02129, USA.
Abstract
Encoding genetic information involves both structure and sequence. Non-protein-coding (NCR) RNAs modulate host immune responses by guiding and assembling stress-specific protein effectors, with flipons enabling dynamic transitions between states. Small NCRs transcribed by both RNA Polymerases 2 and 3 normally modulate these pathways. The miRNAs, tRNA fragments, mitrons, piRNAs, and endo-small-interfering RNA products target the guide effector complexes to their targets. These NCRs filter the subset of RNAs that are translated, a process modulated by other NCRs that fine-tune RNA stability, localization, and kinetics through the modifications they direct. When these RNAs, or their targets, are dysregulated, host interferon responses are activated through the accumulation of uncapped triphosphorylated RNAs, dsRNAs, or flipon-encoded Z-RNAs. These responses are initially suppressed to avoid attacks on self-RNAs, but above a threshold, highly immunogenic pathways are unleashed. These same responses resist viral and other infections without pathogen-specific effectors or prior exposure. They also eliminate dysfunctional cells. These universal responses, when unresolved, contribute to a range of pathologies, increasing cancer, inflammatory diseases, and senescence. The review focuses on recent findings showing how these integrated host responses are driven by, and exploit, the retrotransposon invasion of animal genomes.
Related
- Diversity-generating retroelements enable phages to expand their host range in the human gut.
- Leveraging genomic deep learning models for the prediction of noncoding variant effects
- Total RNA Sequencing Reveals Early Coding, Noncoding, and Isoform-Level Transcriptomic Changes Following Traumatic and Glaucomatous Optic Nerve Injury
- Evaluating the added value of sequence models in noncoding RNA assays: a baseline-aware framework
- Loss of DNA Demethylase Enhances Arsenic Resistance Via Reducing of PIN2 Antisense Long Noncoding RNA
BibTeX
@article{herbert2026flipons,
title = {{Flipons, Noncoding Transcripts and Retroelements: A Universal Host Defense.}},
author = {Alan Herbert},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198526},
url = {https://europepmc.org/article/MED/42883775},
note = {CC BY},
}
RIS
TY - JOUR
TI - Flipons, Noncoding Transcripts and Retroelements: A Universal Host Defense.
AU - Alan Herbert
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198526
UR - https://europepmc.org/article/MED/42883775
AB - Encoding genetic information involves both structure and sequence. Non-protein-coding (NCR) RNAs modulate host immune responses by guiding and assembling stress-specific protein effectors, with flipons enabling dynamic transitions between states. Small NCRs transcribed by both RNA Polymerases 2 and 3 normally modulate these pathways. The miRNAs, tRNA fragments, mitrons, piRNAs, and endo-small-interfering RNA products target the guide effector complexes to their targets. These NCRs filter the subset of RNAs that are translated, a process modulated by other NCRs that fine-tune RNA stability, localization, and kinetics through the modifications they direct. When these RNAs, or their targets, are dysregulated, host interferon responses are activated through the accumulation of uncapped triphosphorylated RNAs, dsRNAs, or flipon-encoded Z-RNAs. These responses are initially suppressed to avoid attacks on self-RNAs, but above a threshold, highly immunogenic pathways are unleashed. These same responses resist viral and other infections without pathogen-specific effectors or prior exposure. They also eliminate dysfunctional cells. These universal responses, when unresolved, contribute to a range of pathologies, increasing cancer, inflammatory diseases, and senescence. The review focuses on recent findings showing how these integrated host responses are driven by, and exploit, the retrotransposon invasion of animal genomes.
SN - 1422-0067
ER -