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Seminar by Marco Marcia (October, 19th 2021), EMBL Grenoble

Amphi Carnot Dr Marco MARCIA EMBL Grenoble, France The multiple dimensions of lncRNAs : How 3D structure determines MEG3 function Abstract: Long non-coding RNAs (lncRNAs) are key regulators of gene expression, playing active roles in epigenetics, transcriptional and translational regulation, and chromatin scaffolding. However, because of their recent discovery and molecular complexity, lncRNAs are still very poorly characterized from a mechanistic perspective raising outstanding biological questions on how they selectively and efficiently tune gene expression. In my lab, we are interested in elucidating the mechanistic complexity of lncRNAs from an interdisciplinary evolutionary, cellular, and structural perspective, including by imaging lncRNAs and their functionally- related proteins in 3D with biophysical and structural biology methods. I will specifically report on how we are dissecting the structural and functional properties of a lncRNA that stimulates the p53 pathway preventing tumorigenesis. This lncRNA adopts a well-defined structural core, dictated by tertiary interactions that are essential for p53 stimulation and for inducing cell cycle arrest. Remarkably, we could recently visualize its 3D shape and topology for the first time by AFM and SAXS at ~15 Å resolution. Our findings connect the 3D structure of a lncRNA to its biological function and open still-unexplored research perspectives to understand lncRNA biology at high-resolution and to exploit their translational potential in RNA-based therapies