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Enders, L.* ; Siklos, M.* ; Borggräfe, J. ; Gaussmann, S. ; Koren, A.* ; Malik, M.* ; Tomek, T.* ; Schuster, M.* ; Reiniš, J.* ; Hahn, E.* ; Rukavina, A.* ; Reicher, A.* ; Casteels, T.* ; Bock, C.* ; Winter, G.E.* ; Hannich, J.T.* ; Sattler, M. ; Kubicek, S.*

Pharmacological perturbation of the phase-separating protein SMNDC1.

Nat. Commun. 14:4504 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
SMNDC1 is a Tudor domain protein that recognizes di-methylated arginines and controls gene expression as an essential splicing factor. Here, we study the specific contributions of the SMNDC1 Tudor domain to protein-protein interactions, subcellular localization, and molecular function. To perturb the protein function in cells, we develop small molecule inhibitors targeting the dimethylarginine binding pocket of the SMNDC1 Tudor domain. We find that SMNDC1 localizes to phase-separated membraneless organelles that partially overlap with nuclear speckles. This condensation behavior is driven by the unstructured C-terminal region of SMNDC1, depends on RNA interaction and can be recapitulated in vitro. Inhibitors of the protein's Tudor domain drastically alter protein-protein interactions and subcellular localization, causing splicing changes for SMNDC1-dependent genes. These compounds will enable further pharmacological studies on the role of SMNDC1 in the regulation of nuclear condensates, gene regulation and cell identity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 14, Heft: 1, Seiten: , Artikelnummer: 4504 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)