Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription

dos Santos, Alia, Rollins, Daniel E., Hari-Gupta, Yukti, McArthur, Hannah, Du, Mingxue, Yong Zi Ru, Sabrina, Pidlisina, Kseniia, Stranger, Ane, Lorgat, Faeeza, Lambert, Danielle, and others. (2023) Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription. Nature Communications, 14 (1). Article Number 2855. E-ISSN 2041-1723. (doi:10.1038/s41467-023-38572-9) (KAR id:101235)

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Official URL: https://doi.org/10.1038/s41467-023-38572-9

Abstract

NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We found that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene-expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation.

Item Type:	Article
DOI/Identification number:	10.1038/s41467-023-38572-9
Additional information:	For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Uncontrolled keywords:	Animals, Mammals, RNA Polymerase II, Nuclear Proteins, DNA, Nucleic Acid Conformation, Autophagy
Subjects:	Q Science
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Funders:	Medical Research Council (https://ror.org/03x94j517)
Depositing User:	Peter Ellis
Date Deposited:	11 May 2023 13:53 UTC
Last Modified:	05 Nov 2024 13:06 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/101235 (The current URI for this page, for reference purposes)

University of Kent Author Information

dos Santos, Alia.

Creator's ORCID:	https://orcid.org/0000-0002-3176-8317
CReDIT Contributor Roles:

McArthur, Hannah.

Creator's ORCID:	https://orcid.org/0000-0002-6046-0012
CReDIT Contributor Roles:

Stranger, Ane.

Creator's ORCID:
CReDIT Contributor Roles:

Brown, Ian R..

Creator's ORCID:	https://orcid.org/0000-0002-6989-4474
CReDIT Contributor Roles:

Howland, Kevin.

Creator's ORCID:	https://orcid.org/0000-0003-4370-0974
CReDIT Contributor Roles:

Ellis, Peter J.I..

Creator's ORCID:	https://orcid.org/0000-0001-9709-7934
CReDIT Contributor Roles:

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