Single-molecule modeling of mRNA degradation by miRNA: Lessons from data.
BMC Syst Biol
; 9 Suppl 3: S2, 2015.
Article
en En
| MEDLINE
| ID: mdl-26050661
ABSTRACT
Recent experimental results on the effect of miRNA on the decay of its target mRNA have been analyzed against a previously hypothesized single molecule degradation pathway. According to that hypothesis, the silencing complex (miRISC) first interacts with its target mRNA and then recruits the protein complexes associated with NOT1 and PAN3 to trigger deadenylation (and subsequent degradation) of the target mRNA. Our analysis of the experimental decay patterns allowed us to refine the structure of the degradation pathways at the single molecule level. Surprisingly, we found that if the previously hypothesized network was correct, only about 7% of the target mRNA would be regulated by the miRNA mechanism, which is inconsistent with the available knowledge. Based on systematic data analysis, we propose the alternative hypothesis that NOT1 interacts with miRISC before binding to the target mRNA. Moreover, we show that when miRISC binds alone to the target mRNA, the mRNA is degraded more slowly, probably through a deadenylation-independent pathway. The new biochemical pathway proposed here both fits the data and paves the way for new experimental work to identify new interactions.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Análisis de Sistemas
/
ARN Mensajero
/
Proteínas Portadoras
/
Estabilidad del ARN
/
Proteínas de Drosophila
/
MicroARNs
/
Modelos Biológicos
Límite:
Animals
Idioma:
En
Revista:
BMC Syst Biol
Asunto de la revista:
BIOLOGIA
/
BIOTECNOLOGIA
Año:
2015
Tipo del documento:
Article