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Study of the role of RNA methylation in transposable element control during aging (RNAMETAGEING)

21st national competition for scientific and technical research

Aging and neurodegenerative diseases

Senior Researcher : Diana Guallar Artal

Research Centre or Institution : Universidad de Santiago de Compostela.

Abstract

Aging is a complex multifactorial process shared by all living organisms, which represents the greatest risk factor for most human diseases in western societies. Despite the great number of studies in ageing, its intrinsic complexity has hindered the development of successful clinical strategies to counterbalance it. At the cellular level, ageing is accompanied by a global loss of repressive epigenetic marks, which lead to the aberrant expression of unwanted genomic loci such as transposable elements (TEs). 

The Epitranscriptome, which refers to chemical modifications on RNA, plays key functions in all steps of RNA biology, and its deregulation is linked to age-related disorders. While my preliminary data shows that TE RNAs can be methylated (m5C), and that proteins involved in m5C regulation are altered in ageing, the contribution of this epitranscriptomic mark to TE alteration with age remains currently unexplored. The RNAMETAGEING project proposes to take a novel approach to investigate TE deregulation linked to ageing through the lenses of Epitranscriptomics. For this purpose, we will characterize through system-wide approaches (1) the distribution and dynamics of m5C modification in TE RNAs during ageing, and (2) the key regulators that orchestrate m5C modification in TE RNA molecules. Given that RNA methylation is reversible, I propose to dissect the minimal combination of epitranscriptomic modulators that could be used to reverse ageing hallmarks in vitro through TE modulation. The RNAMETAGEING project will elucidate novel mechanisms of ageing that will provide with novel biomarkers and strategies to tackle this, yet, unavoidable consequence of life.

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