MiRNAs confer phenotypic robustness to gene networks by suppressing biological noise.
Nat Commun
; 4: 2364, 2013.
Article
en En
| MEDLINE
| ID: mdl-24077216
ABSTRACT
miRNAs are small non-coding RNAs able to modulate target gene expression. It has been postulated that miRNAs confer robustness to biological processes, but clear experimental evidence is still missing. Here, using a synthetic biological approach, we demonstrate that microRNAs provide phenotypic robustness to transcriptional regulatory networks by buffering fluctuations in protein levels. We construct a network motif in mammalian cells exhibiting a 'toggle-switch' phenotype in which two alternative protein expression levels define its ON and OFF states. The motif consists of an inducible transcription factor that self-regulates its own transcription and that of a miRNA against the transcription factor itself. We confirm, using mathematical modelling and experimental approaches, that the microRNA confers robustness to the toggle-switch by enabling the cell to maintain and transmit its state. When absent, a dramatic increase in protein noise level occurs, causing the cell to randomly switch between the two states.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Retroalimentación Fisiológica
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MicroARNs
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Factor de Transcripción E2F1
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Redes Reguladoras de Genes
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Modelos Genéticos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2013
Tipo del documento:
Article