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H2020Individual fellowship2015–2017

RncRNAA · Functions of non-coding RNAs in protein synthesis and homeostasis during aging

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2015-04-01 → 2017-03-31
EU contribution
€159,461
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

Functions of non-coding RNAs in protein synthesis and homeostasis during aging

1a) What is the problem/issue being addressed? Reduction of the Insulin / Insulin Growth Factor Signaling pathway (IIS) is known to increase lifespan in multiple species. Under normal physiological conditions IIS regulates a multitude of processes, including development, growth, metabolism, stress resistance and reproduction. Which of these mechanisms are involved in the regulation of lifespan in IIS mutants remains to be elucidated. An important factor in growth and metabolism is translation, the production of proteins in the cell by ribosomes. In the C. elegans IIS mutant daf-2, translation is reduced and lifespan increased through a highly upregulated ribosome bound non-coding RNA, tts-1. We set out to determine whether this mechanism is conserved to Drosophila and mouse IIS mutants. 1b) Why is it important for society? The average age in modern societies has been steadily rising for at least last half a century. The burden on society of age-related diseases has increased accordingly. It is therefore key to determine what underlying mechanisms regulate healthy ageing and how they can be manipulated to maintain better health in old age. 1c) What are the overall objectives? We aimed to discover whether translation is decreased in Drosophila and mouse IIS mutants and whether this is regulated by ncRNAs with a function similar to tts-1.

Data: CORDIS, © European Union

Project objective

Because old age is the largest risk factor for many human diseases, it is one of the key challenges of our time to find ways to increase healthy lifespan and reduce the loss of health in later life. Inhibition of protein synthesis is capable of extending the lifespan of a number of organisms and has been shown to ameliorate symptoms in models of several age related diseases. Recent studies have shown that non-coding (nc) RNAs frequently interact with translating ribosomes, although little is known about their function there. In previous work, I discovered a ribosome-bound ncRNA to be required for both the inhibition of translation and the increase in lifespan seen in insulin signaling (IIS) mutant worms. However, due to a nematode-specific RNA trans-splicing mechanism, affecting post-transcriptional gene regulation, the relevance of these results to others organisms remains unclear.Given the crucial role protein synthesis plays in lifespan determination and the unexplored functions of ncRNAs in this process, I propose to systematically investigate the role of ncRNAs in translation and longevity. My goal is to identify ncRNAs that interact with ribosomes that have an effect on proteostasis or post-transcriptional gene regulation and consequently on lifespan extension and understanding their function.

Original text from CORDIS.

Participants

  • MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENCoordinatorGermany

Links

Data: CORDIS, © European Union