Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex.

Autor:	Dubiez E; European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; Univ. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France., Pellegrini E; European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France., Finderup Brask M; Department of Molecular Biology and Genetics, Universitetsbyen 81, Aarhus University, Aarhus, Denmark., Garland W; Department of Molecular Biology and Genetics, Universitetsbyen 81, Aarhus University, Aarhus, Denmark., Foucher AE; Univ. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France., Huard K; European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France., Heick Jensen T; Department of Molecular Biology and Genetics, Universitetsbyen 81, Aarhus University, Aarhus, Denmark., Cusack S; European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France. Electronic address: cusack@embl.fr., Kadlec J; Univ. Grenoble Alpes, CNRS, CEA, IBS, 38000 Grenoble, France. Electronic address: jan.kadlec@ibs.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jan 23; Vol. 43 (1), pp. 113639. Date of Electronic Publication: 2024 Jan 04.
DOI:	10.1016/j.celrep.2023.113639
Abstrakt:	The nuclear cap-binding complex (CBC) coordinates co-transcriptional maturation, transport, or degradation of nascent RNA polymerase II (Pol II) transcripts. CBC with its partner ARS2 forms mutually exclusive complexes with diverse "effectors" that promote either productive or destructive outcomes. Combining AlphaFold predictions with structural and biochemical validation, we show how effectors NCBP3, NELF-E, ARS2, PHAX, and ZC3H18 form competing binary complexes with CBC and how PHAX, NCBP3, ZC3H18, and other effectors compete for binding to ARS2. In ternary CBC-ARS2 complexes with PHAX, NCBP3, or ZC3H18, ARS2 is responsible for the initial effector recruitment but inhibits their direct binding to the CBC. We show that in vivo ZC3H18 binding to both CBC and ARS2 is required for nuclear RNA degradation. We propose that recruitment of PHAX to CBC-ARS2 can lead, with appropriate cues, to competitive displacement of ARS2 and ZC3H18 from the CBC, thus promoting a productive rather than a degradative RNA fate. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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