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M5C RNA

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Cytosine 5 methylated RNAs as stem cell regulators in normal tissues and disease...

Cytosine 5 methylated RNAs as stem cell regulators in normal tissues and diseases Stem cells differentiate into all mammalian tissues and organs during development, and remain present to maintain and replenish tissues throughout life. Stem cells continuously maintain their population (self-renewal) while gener... ver más

31/01/2018

THE CHANCELLOR MAS...

1M€

Presupuesto del proyecto: 1M€

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THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2018-01-31 No tenemos la información de la convocatoria

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Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

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Descripción del proyecto Stem cells differentiate into all mammalian tissues and organs during development, and remain present to maintain and replenish tissues throughout life. Stem cells continuously maintain their population (self-renewal) while generating progeny (differentiation). During self-renewal stem cells have to avoid cell cycle exit and differentiation; whereas during differentiation stem cells must evade uncontrolled proliferation. Dissecting the regulatory pathways controlling the balance between these two states is fundamental to understanding how stem cell mis-regulation causes human diseases. Although transcriptional regulation of stem cells is increasingly understood, virtually nothing is known about how post-transcriptional mechanisms can influence stem cell maintenance. Post-transcriptional modifications are commonly found in non-coding RNA species, yet the biological function is unknown. My previous studies identified cytosine-5 methylation (m5C) of RNA as a novel mechanism regulating stem cell fate. m5C is a widespread modification in both DNA and RNAs and their methyltransferases share many structural features. Whereas the functions of m5C in DNA have been extensively studied, the cellular and molecular functions of the same modified nucleobase in RNA remain unclear. Using a combination of system-wide approaches, mouse models and in vitro differentiation assays, we propose to (1) globally identify m5C in RNA species; (2) functionally analyze the roles of methylated versus non-methylated RNAs in stem cells; and (3) determine how aberrant m5C modifications can cause intellectual disability disorders in humans. Our comprehensive approach will answer how post-transcriptional modification control stem cell fate in normal tissues and might lead to the discovery of novel therapeutic strategies for neurological disorders in humans.

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