Journal article
Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and Ras Is Conserved Across Species
Genetics (Austin), Vol.203(2), pp.749-762
03/30/2016
DOI: 10.1534/genetics.116.187930
PMCID: PMC4896191
PMID: 27029730
Abstract
Dis3 encodes a conserved RNase that degrades or processes all RNA species via an N-terminal PilT N terminus (PIN) domain and C-terminal RNB domain that harbor, respectively, endonuclease activity and 3′–5′ exonuclease activity. In
Schizosaccharomyces pombe
,
dis3
mutations cause chromosome missegregation and failure in mitosis, suggesting
dis3
promotes cell division. In humans, apparently hypomorphic
dis3
mutations are found recurrently in multiple myeloma, suggesting
dis3
opposes cell division. Except for the observation that RNAi-mediated depletion of
dis3
function drives larval arrest and reduces tissue growth in
Drosophila
, the role of
dis3
has not been rigorously explored in higher eukaryotic systems. Using the
Drosophila
system and newly generated
dis3
null alleles, we find that absence of
dis3
activity inhibits cell division. We uncover a conserved CDK1 phosphorylation site that when phosphorylated inhibits Dis3’s exonuclease, but not endonuclease, activity. Leveraging this information, we show that Dis3’s exonuclease function is required for mitotic cell division: in its absence, cells are delayed in mitosis and exhibit aneuploidy and overcondensed chromosomes. In contrast, we find that modest reduction of
dis3
function enhances cell proliferation in the presence of elevated Ras activity, apparently by accelerating cells through G2/M even though each insult by itself delays G2/M. Additionally, we find that
dis3
and
ras
genetically interact in worms and that
dis3
can enhance cell proliferation under growth stimulatory conditions in murine B cells. Thus, reduction, but not absence, of
dis3
activity can enhance cell proliferation in higher organisms.
Details
- Title: Subtitle
- Collaborative Control of Cell Cycle Progression by the RNA Exonuclease Dis3 and Ras Is Conserved Across Species
- Creators
- Mark J. Snee - Washington University in St. LouisWilliam C. Wilson - Washington University in St. LouisYi Zhu - Washington University in St. LouisShin-Yu Chen - The University of Texas MD Anderson Cancer CenterBeth A. Wilson - Washington University in St. LouisCedric Kseib - The University of Texas MD Anderson Cancer CenterJulie O’Neal - Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110Nitin Mahajan - Washington University in St. LouisMichael H. Tomasson - Washington University in St. LouisSwathi Arur - The University of Texas MD Anderson Cancer CenterJames B. Skeath - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.203(2), pp.749-762
- Publisher
- Genetics Society of America
- DOI
- 10.1534/genetics.116.187930
- PMID
- 27029730
- PMCID
- PMC4896191
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Language
- English
- Date published
- 03/30/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984359953402771
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