Structure-aware machine learning identifies microRNAs operating as Toll-like receptor 7/8 ligands.
RNA Biol
; 18(sup1): 268-277, 2021 10 15.
Article
en En
| MEDLINE
| ID: mdl-34241565
ABSTRACT
MicroRNAs (miRNAs) can serve as activation signals for membrane receptors, a recently discovered function that is independent of the miRNAs' conventional role in post-transcriptional gene regulation. Here, we introduce a machine learning approach, BrainDead, to identify oligonucleotides that act as ligands for single-stranded RNA-detecting Toll-like receptors (TLR)7/8, thereby triggering an immune response. BrainDead was trained on activation data obtained from in vitro experiments on murine microglia, incorporating sequence and intra-molecular structure, as well as inter-molecular homo-dimerization potential of candidate RNAs. The method was applied to analyse all known human miRNAs regarding their potential to induce TLR7/8 signalling and microglia activation. We validated the predicted functional activity of subsets of high- and low-scoring miRNAs experimentally, of which a selection has been linked to Alzheimer's disease. High agreement between predictions and experiments confirms the robustness and power of BrainDead. The results provide new insight into the mechanisms of how miRNAs act as TLR ligands. Eventually, BrainDead implements a generic machine learning methodology for learning and predicting the functions of short RNAs in any context.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligonucleótidos
/
Regulación de la Expresión Génica
/
Microglía
/
MicroARNs
/
Receptor Toll-Like 7
/
Receptor Toll-Like 8
/
Aprendizaje Automático
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
RNA Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania