Annuaire
Nick Gilbert (Professor of Chromatin Biology, Medical Research Council Human Genetics Unit at the University of Edinburgh)
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Le 06/05/2022, de 11:00 à 12:00 |
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| S'adresser à | Salle des Thèses, Equipe Bernard |
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Contact : Vincent Vanoosthuyse
Mammalian transcripts are processed to form abundant chromatin-associated RNAs (caRNA) with a half-life of 60 min; they interact with HNRNPU (also called SAF-A, scaffold attachment factor A) to create a protein/RNA mesh (1) that regulates large-scale chromatin structures (2). Using super-resolution microscopy we show this mesh forms a net comprised of 80-nm SAF-A clusters interacting with thread-like filaments, separating transcriptionally active regions from the nucleoplasm. Transcription inhibition, triggering caRNA degradation, causes the mesh to collapse, compacting chromatin, and is re-created by polymer model simulations. Under normal conditions the caRNA mesh is rapidly turned over by XRN2, a HNRNPU interacting protein. XRN2 depletion maintains caRNA levels, even after transcription inhibition, and retains chromatin in a decompacted configuration. However, loss of XRN2 and a build-up of caRNA triggers a DNA damage response. Surprisingly, caRNA degradation by XRN2 sustains the ribonucleotide pool, and in its absence causes transcription inhibition. For the first time we show that caRNAs both perform a structural role regulating chromosome structure but are also recycled by XRN2, linking together chromatin architecture and transcriptional regulation.
(1) Marenda M, Lazarova E, van de Linde S, Gilbert N, Michieletto D. Parameter-free molecular super-structures quantification in single-molecule localization microscopy. J Cell Biol. 2021 220(5):e202010003.
(2) Nozawa RS, Boteva L, Soares DC, Naughton C, Dun AR, Buckle A, Ramsahoye B, Bruton PC, Saleeb RS, Arnedo M, Hill B, Duncan RR, Maciver SK, Gilbert N. SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs. Cell. 2017 169:1214-1227