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

Author

Listed:
  • Ália dos Santos

    (University of Sheffield
    MRC LMB, Francis Crick Avenue)

  • Daniel E. Rollins

    (University of Sheffield)

  • Yukti Hari-Gupta

    (University of Kent
    MRC LMCB, University College London)

  • 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

    (HHMI Janelia Research Campus)

  • Lin Wang

    (Central Laser Facility, Research Complex at Harwell, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell, Didcot)

  • Peter J. I. Ellis

    (University of Kent)

  • Teng-Leong Chew

    (HHMI Janelia Research Campus)

  • Marisa Martin-Fernandez

    (Central Laser Facility, Research Complex at Harwell, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell, Didcot)

  • Alice L. B. Pyne

    (University of Sheffield)

  • Christopher P. Toseland

    (University of Sheffield)

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.

Suggested Citation

  • Ália dos Santos & Daniel E. Rollins & Yukti Hari-Gupta & Hannah McArthur & Mingxue Du & Sabrina Yong Zi Ru & Kseniia Pidlisna & Ane Stranger & Faeeza Lorgat & Danielle Lambert & Ian Brown & Kevin Howl, 2023. "Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38572-9
    DOI: 10.1038/s41467-023-38572-9
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    References listed on IDEAS

    as
    1. Yukti Hari-Gupta & Natalia Fili & Ália dos Santos & Alexander W. Cook & Rosemarie E. Gough & Hannah C. W. Reed & Lin Wang & Jesse Aaron & Tomas Venit & Eric Wait & Andreas Grosse-Berkenbusch & J. Chri, 2022. "Myosin VI regulates the spatial organisation of mammalian transcription initiation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Byeong-Won Kim & Seung Beom Hong & Jun Hoe Kim & Do Hoon Kwon & Hyun Kyu Song, 2013. "Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
    3. Benjamin R. Schrank & Tomas Aparicio & Yinyin Li & Wakam Chang & Brian T. Chait & Gregg G. Gundersen & Max E. Gottesman & Jean Gautier, 2018. "Nuclear ARP2/3 drives DNA break clustering for homology-directed repair," Nature, Nature, vol. 559(7712), pages 61-66, July.
    4. Natalia Fili & Yukti Hari-Gupta & Ália dos Santos & Alexander Cook & Simon Poland & Simon M. Ameer-Beg & Maddy Parsons & Christopher P. Toseland, 2017. "NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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