Eukaryotic Regulated RNA Catabolism
Start date: Apr 1, 2014,
End date: Mar 31, 2019
"Regulation and fidelity of gene expression is fundamental to the differentiation and maintenance of all living organisms. While historically attention has been focused on the process of transcriptional activation, we predict that RNA turnover pathways are equally important for gene expression regulation. This has been implied for selected protein-coding RNAs (mRNAs) but is virtually unexplored for non-protein-coding RNAs (ncRNAs).The intention of the EURECA proposal is to establish cutting-edge research to characterize mammalian nuclear RNA turnover; its factor utility, substrate specificity and regulatory capacity. We foresee that RNA turnover is at the core of gene expression regulation - forming intricate connection to RNA productive systems – thus, being centrally placed to determine RNA fate. EURECA seeks to dramatically improve our understanding of cellular decision processes impacting RNA levels and to establish models for how regulated RNA turnover helps control key biological processes.The realization that the number of ncRNA producing genes was previously grossly underestimated foretells that ncRNA regulation will impact on most aspects of cell biology. Consistently, aberrant ncRNA levels correlate with human disease phenotypes and RNA turnover complexes are linked to disease biology. Still, solid models for how ncRNA turnover regulate biological processes in higher eukaryotes are not available. Moreover, which ncRNAs retain function and which are merely transcriptional by-products remain a major challenge to sort out. The circumstances and kinetics of ncRNA turnover are therefore important to delineate as these will ultimately relate to the likelihood of molecular function. A fundamental challenge here is to also discern which protein complements of non-coding ribonucleoprotein particles (ncRNPs) are (in)compatible with function. Balancing single transcript/factor analysis with high-throughput methodology, EURECA will address these questions."
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