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Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper

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posted on 2023-06-08, 20:14 authored by Joseph A Waldron, Chris JonesChris Jones, Benjamin P Towler, Amy L Pashler, Dominic P Grima, Stephen Hebbes, Samuel H Crossman, Maria V Zabolotskaya, Sarah NewburySarah Newbury
Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms.

Funding

G0045-03; BBSRC; BB/G002754/1

MRC 2010 DTA; G0625; MRC-MEDICAL RESEARCH COUNCIL; G1000409

2011 Doctoral Training Grant (MRC): Centenary Award Supplement; G0947; MRC-MEDICAL RESEARCH COUNCIL; Supplement to MR/J500525/1 G0655

Biochemical Society

G0056-02; BBSRC; BB/I021345/1

Nuffield Foundation; URB/39931

History

Publication status

  • Published

File Version

  • Published version

Journal

Biology Open

ISSN

2046-6390

Publisher

The Company of Biologists Ltd.

Volume

4

Page range

649-660

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-03-06

First Open Access (FOA) Date

2015-03-06

First Compliant Deposit (FCD) Date

2015-03-06

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