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R&D activities program between research groups on Biomedicine 2017
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RNA & RNA binding Proteins: Implications in diSease and hEalth

B2017/BMD-3770

Graphical Abstract

The RyPSE program tackles a key theme in Biomedicine: the impact of RNA biology in health and disease. Living cells contain various types of RNAs performing specific cellular functions, linked to dysfunctions that are in the origin of pathologic processes. To grasp the molecular basis of disease is fundamental to understand the mechanisms operating in healthy cells. Frequently the difference between health and disease could be traced to alterations in the networks of particular RNAs with RNA-binding proteins (RBPs), other RNAs or DNA. Both RPBs and messenger RNAs (mRNAs) regulate gene expression at posttranscriptional level. Failure of RBP function can lead to syndromes like Spinal Muscular Atrophy (SMA) o Amyotrophic Lateral Sclerosis (ALS). Additionally, mutations on the mRNA alter its structure and its translation outcome causing diseases like X-Fragile syndrome and Hungtinton. Human pathogens like HCV, HIV or PB, govern viral protein synthesis through structural elements on its RNAs (IRES) assisted by RBPs. Thus, knowledge of the IRES mechanism of action is essential to combat these pathogens. Besides mRNAs, there are multiple non-coding transcripts in the cell. Relevant examples are the lncRNAs TERRA transcribed from the telomere, implicated in cellular ageing and cancer. In this project we propose to tackle the analysis of RNA-protein complexes from a multidisciplinary perspective, including coordination chemistry, molecular and cell biology, and structural biology. We have selected target molecules - RNAs and RBPs – that are main characters in essential cellular processes (telomere length maintenance in eukaryotic chromosomes, control of protein synthesis in non-conventional mRNAs). Inappropriate function of these molecules is associated to neurodegenerative diseases, infections, cancer and aging.

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Upcoming meetings of interest!!

EMBO meeting: Protein Synthesis and translational control