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SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES

Susanne Leidescher, Johannes Nübler, Yana Feodorova, Erica Hildebrand, Simon Ullrich, Sebastian Bultmann, Stephanie Link, Katharina Thanisch, Job Dekker, Heinrich Leonhardt, Leonid Mirny, Irina Solovei
doi: https://doi.org/10.1101/2020.05.20.106591
Susanne Leidescher
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
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Johannes Nübler
2Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Yana Feodorova
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
3Department of Medical Biology, Medical University of Plovdiv; Division of Molecular and Regenerative Medicine, Research Institute at Medical University of Plovdiv, Boulevard Vasil Aprilov 15A, Plovdiv 4000, Bulgaria
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Erica Hildebrand
4Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Simon Ullrich
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
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Sebastian Bultmann
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
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Stephanie Link
5BioMedizinisches Center, Ludwig-Maximilians University Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany
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Katharina Thanisch
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
6Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riss, Germany
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Job Dekker
4Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
7Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
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Heinrich Leonhardt
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
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Leonid Mirny
2Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Irina Solovei
1Department of Biology II, Biozentrum, Ludwig-Maximilians University Munich (LMU), Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
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  • For correspondence: Irina.Solovei@lrz.uni-muenchen.de
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SUMMARY

Despite the well established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are still poorly understood. Here, we make use of several long highly expressed mammalian genes and demonstrate that they form Transcription Loops (TLs) with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. TLs dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness. Both experimental evidence and polymer modeling support the hypothesis that TL stiffness is caused by the dense decoration of transcribed genes with multiple voluminous nascent RNPs. We propose that TL formation is a universal principle of eukaryotic gene expression.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 21, 2020.
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SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES
Susanne Leidescher, Johannes Nübler, Yana Feodorova, Erica Hildebrand, Simon Ullrich, Sebastian Bultmann, Stephanie Link, Katharina Thanisch, Job Dekker, Heinrich Leonhardt, Leonid Mirny, Irina Solovei
bioRxiv 2020.05.20.106591; doi: https://doi.org/10.1101/2020.05.20.106591
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SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES
Susanne Leidescher, Johannes Nübler, Yana Feodorova, Erica Hildebrand, Simon Ullrich, Sebastian Bultmann, Stephanie Link, Katharina Thanisch, Job Dekker, Heinrich Leonhardt, Leonid Mirny, Irina Solovei
bioRxiv 2020.05.20.106591; doi: https://doi.org/10.1101/2020.05.20.106591

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