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A Novel Role for the 3 5 Exoribonuclease Dis3L2 in Controlling Cell Proliferation and Tissue Growth.pdf (1.4 MB)

A novel role for the 3'-5' exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth

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posted on 2023-06-09, 03:04 authored by Benjamin TowlerBenjamin Towler, Chris JonesChris Jones, Kirsty L Harper, Joseph A Waldron, Sarah NewburySarah Newbury
In a complex organism, cell proliferation and apoptosis need to be precisely controlled in order for tissues to develop correctly. Excessive cell proliferation can lead to diseases such as cancer. We have shown that the exoribonuclease Dis3L2 is required for the correct regulation of proliferation in a natural tissue within the model organism Drosophila melanogaster. Dis3L2 is a member of a highly conserved family of exoribonucleases that degrade RNA in a 3'-5' direction. We show that knockdown of dis3L2 in the Drosophila wing imaginal discs results in substantial wing overgrowth due to increased cellular proliferation rather than an increase in cell size. Imaginal discs are specified in the embryo before proliferating and differentiating to form the adult structures of the fly. Using RNA-seq we identified a small set of mRNAs that are sensitive to Dis3L2 activity. Of the mRNAs which increase in levels and are therefore potential targets of Dis3L2, we identified 2 that change at the post-transcriptional level but not at the transcriptional level, namely CG2678 (a transcription factor) and pyrexia (a TRP cation channel). We also demonstrate a compensatory effect between Dis3L2 and the 5'-3' exoribonuclease Pacman demonstrating that these 2 exoribonucleases function to regulate opposing pathways within the developing tissue. This work provides the first description of the molecular and developmental consequences of Dis3L2 inactivation in a non-human animal model. The work is directly relevant to the understanding of human overgrowth syndromes such as Perlman syndrome.

Funding

PhD studentship; WC003-11; BSMS; WC003-11

Analysis of the nucleotidyltransferase Monkeyking in the control of cell proliferation in Drosophi; G1350; BIOCHEMICAL SOCIETY

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

Epigenetic regulation of gene expression by the exoribonuclease pacman; G0056; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/I021345/1

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

History

Publication status

  • Published

File Version

  • Accepted version

Journal

RNA Biology

ISSN

1547-6286

Publisher

Taylor & Francis

Issue

12

Volume

13

Page range

1286-1299

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-09-22

First Open Access (FOA) Date

2017-09-15

First Compliant Deposit (FCD) Date

2016-09-22

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