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

Towler, Benjamin P, Jones, Christopher L, Harper, Kirsty L, Waldron, Joseph A and Newbury, Sarah F (2016) A novel role for the 3′-5′ exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth. RNA Biology, 13 (12). pp. 1286-1299. ISSN 1547-6286

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Abstract

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0470.A-Z Experimental organisms, A-Z > QH0470.D7 Drosophila
Q Science > QH Natural history > QH0301 Biology
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0460 Mutations
Q Science > QL Zoology > QL0360 Invertebrates
Depositing User: Sarah Newbury
Date Deposited: 22 Sep 2016 11:19
Last Modified: 15 Mar 2017 02:18
URI: http://sro.sussex.ac.uk/id/eprint/63526

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Project NameSussex Project NumberFunderFunder Ref
Epigenetic regulation of gene expression by the exoribonuclease pacmanG0056BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/I021345/1
PhD studentshipWC003-11BSMSWC003-11
MRC 2010 DTAG0625MRC-MEDICAL RESEARCH COUNCILG1000409
2011 Doctoral Training Grant (MRC): Centenary Award SupplementG0947MRC-MEDICAL RESEARCH COUNCILSupplement to MR/J500525/1 G0655
Analysis of the nucleotidyltransferase Monkeyking in the control of cell proliferation in DrosophiG1350BIOCHEMICAL SOCIETYUnset