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The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation

Chaves-Arquero, B; Collins, K; Christodoulou, E; Nicastro, G; Martin, SR; Ramos, A; (2021) The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation. RNA Biology 10.1080/15476286.2021.1991169. (In press). Green open access

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Abstract

TUT4 and the closely related TUT7 are non-templated poly(U) polymerases required at different stages of development, and their mis-regulation or mutation has been linked to important cancer pathologies. While TUT4(7) interaction with its pre-miRNA targets has been characterized in detail, the molecular bases of the broader target recognition process are unclear. Here, we examine RNA binding by the ZnF domains of the protein. We show that TUT4(7) ZnF2 contains two distinct RNA binding surfaces that are used in the interaction with different RNA nucleobases in different targets, i.e that this small domain encodes diversity in TUT4(7) selectivity and molecular function. Interestingly and unlike other well-characterized CCHC ZnFs, ZnF2 is not physically coupled to the flanking ZnF3 and acts independently in miRNA recognition, while the remaining CCHC ZnF of TUT4(7), ZnF1, has lost its intrinsic RNA binding capability. Together, our data suggest that the ZnFs of TUT4(7) are independent units for RNA and, possibly, protein-protein interactions that underlay the protein’s functional flexibility and are likely to play an important role in building its interaction network.

Type: Article
Title: The distinct RNA-interaction modes of a small ZnF domain underlay TUT4(7) diverse action in miRNA regulation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/15476286.2021.1991169
Publisher version: https://doi.org/10.1080/15476286.2021.1991169
Language: English
Additional information: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: TUT4/zcchc11; pre-let7i miRNA; ssRNA recognition; nuclear magnetic resonance; Biolayer Interferometry
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10137697
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