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Interplays between miRNAs and transcription factors in the determination and mai...

Interplays between miRNAs and transcription factors in the determination and maintenance of cell identity "miRNAs are small RNAs that guide the RNA-induced silencing complex to mRNA targets, destabilizing them and inhibiting their translation. Much has been learned about their involvement in organism development and function, yet some... ver más

31/10/2015

UNIVERSITAT BASEL

892K€

Presupuesto del proyecto: 892K€

Líder del proyecto

UNIVERSITAT BASEL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2015-10-31 No tenemos la información de la convocatoria

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1 Participantes

UNIVERSITAT BASEL

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Líder del proyecto

UNIVERSITAT BASEL No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 892K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "miRNAs are small RNAs that guide the RNA-induced silencing complex to mRNA targets, destabilizing them and inhibiting their translation. Much has been learned about their involvement in organism development and function, yet some striking puzzles remain. On the one hand it has been shown that miRNAs are essential for development, and the preferential targeting of transcription factors (TFs) by miRNAs suggests that miRNAs and TFs ""coordinate"" to regulate gene expression. Furthermore, studies in the past year concluded that, on their own or in combination with TFs, miRNAs can induce reprogramming of somatic cells into induced pluripotent stem cells (iPSC). On the other hand, high-throughput measurements of mRNA and protein level changes upon miRNA transfections suggest that miRNAs have largely a ""fine-tuning"" function. These small effects on individual genes must, however, confer a substantial selective advantage, because many target sites remain conserved over long evolutionary distances. Here I first propose to investigate the hypothesis that instead of primarily affecting the average levels of target genes, miRNAs reduce the cell-to-cell variation in gene expression, affecting precisely the steps that determine the intrinsic noise. I will then use miRNA-mediated reprogramming of somatic cells into iPSCs as a model system to directly investigate the ""coordination"" between miRNAs and TFs in determining cell identity and differentiation. Through determination of miRNA targets with Argonaute crosslinking and immunoprecipitation, mRNA sequencing and methylated DNA immunoprecipitation I attempt to retrace the regulatory interactions that lead from induction of a few miRNAs, through perturbation of TF activities, to the activation of ""stemness"" genes. Finally, following up on preliminary results obtained in my lab, I will investigate the function of miRNA targeting in the nucleus, that potentially couples transcriptional and post-transcriptional regulation more directly."

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