A ubiquitous disordered protein interaction module
orchestrates transcription elongation
K. Čermáková1, J. Demeulemeester2,
V. Lux3 , M. Nedomová3 , S.R. Goldman4 , E.A.
Smith1 , P. Srb3 , R. Hexnerová3 , M. Fábry3
, M. Mádliková3 , M. Hořejší3 , J.DeRijck 5 ,
Z. Debyser2, , K. Adelman4, H.C. Hodges1, V.
Veverka3,6
1Center for Precision
Environmental Health, Department of Molecular and Cellular Biology, and Dan L
Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX,
USA.
2SMolecular Virology
and Gene Therapy, KU Leuven, Leuven, Flanders, Belgium.
Present address: The Francis Crick Institute, London, UK.
3Institute of Organic
Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech
Republic
4Department of
Biological Chemistry and Molecular Pharmacology, Harvard Medical School,
Boston, MA, USA
5Molecular Virology and
Gene Therapy, KU Leuven, Leuven, Flanders, Belgium.
6Department of Cell
Biology, Faculty of Science, Charles University, Prague, Czech Republic.
vaclav.veverka@uochb.cas.cz
During eukaryotic transcription elongation,
RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we
identified a common binary interaction module consisting of TFIIS N-terminal
domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This
module was conserved among the elongation machinery and linked complexes
including transcription factor TFIIS, Mediator, super elongation complex,
elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other
factors. Using nuclear magnetic resonance, live-cell microscopy, and mass
spectrometry, we revealed the structural basis for these interactions and found
that TND-TIM sequences were necessary and sufficient to induce strong and
specific colocalization in the crowded nuclear environment. Disruption of a
single TIM in IWS1 induced robust changes in gene expression and RNAP2
elongation dynamics, which underscores the functional importance of TND-TIM
surfaces for transcription elongation.The references
should be listed immediately at the end of text without a heading.
1.Cermakova et. al, .Science, 374, (2021),
1113-1121.