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

DOI: 10.1038/s41467-023-38572-9

Authors: Ália Dos Santos (University of Sheffield) , Daniel E. Rollins (University of Sheffield) , Yukti Hari-Gupta (University of Kent) , Hannah Mcarthur (University of Kent) , Mingxue Du (University of Sheffield) , Sabrina Yong Zi Ru (University of Kent) , Kseniia Pidlisna (University of Kent) , Ane Stranger (University of Kent) , Faeeza Lorgat (University of Sheffield) , Danielle Lambert (University of Sheffield) , Ian Brown (University of Kent) , Kevin Howland (University of Kent) , Jesse Aaron (Advanced Imaging Center) , Lin Wang (Central Laser Facility, Research Complex at Harwell) , Peter J. I. Ellis (University of Kent) , Teng-Leong Chew (Advanced Imaging Center) , Marisa Martin-Fernandez (Central Laser Facility, Science and Technology Facilities Council) , Alice L. B. Pyne (University of Sheffield) , Christopher P. Toseland (University of Sheffield)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 14

State: Published (Approved)
Published: May 2023
Diamond Proposal Number(s): 16207

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 find 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.

Journal Keywords: DNA; DNA-binding proteins; Nanoscale biophysics; Nuclear organization; Super-resolution microscopy

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 24/05/2023 14:13

Discipline Tags:

Biochemistry Chemistry Biophysics Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)