Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Nudt3 is a mRNA Decapping Enzyme That Modulates Cell Migration

ABSTRACT: The Dcp2 and Nudt16 Nudix hydrolases, are mRNA decapping enzymes that preferentially modulate stability of a subset of mRNAs. Here we report Nudt3 is a third Nudix protein that possess mRNA decapping activity in cells and is a modulator of cell migration in MCF-7 breast cancer cells. Genome-wide analysis of Nudt3 compromised cells identified increases in mRNAs involved in cell motility including integrin Î²6, lipocalin-2 and fibronectin. The increase in mRNA levels was dependent on Nudt3 decapping activity where integrin Î²6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled. Moreover, increased cell migration observed in Nudt3 depleted cells was mediated through the extracellular integrin Î²6 and fibronectin protein nexus. We conclude, Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals. Stably transformed MCF-7 cell lines constitutively expressing either a short hairpin RNA (shRNA) directed against Nudt3 (Nudt3KD) or a non-targeted control shRNA (ConKD) were used, with three replicate cultures used per group (n=3).

ORGANISM(S): Homo sapiens

SUBMITTER: Ronald Hart

PROVIDER: E-GEOD-75146 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Nudt3 is an mRNA decapping enzyme that modulates cell migration.

Grudzien-Nogalska Ewa E Jiao Xinfu X Song Man-Gen MG Hart Ronald P RP Kiledjian Megerditch M

RNA (New York, N.Y.) 20160301 5

Removal of the 5'-end 7-methylguanosine cap structure is a critical step in the highly regulated process of mRNA decay. The Nudix hydrolase, Dcp2, was identified as a first decapping enzyme and subsequently shown to preferentially modulate stability of only a subset of mRNAs. This observation led to the hypothesis that mammalian cells possess multiple decapping enzymes that may function in distinct pathways. Here we report Nudt3 is a Nudix protein that possesses mRNA decapping activity in cells ...[more]

PMID: 26932476

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Project description:TGFBR1*6A is a common hypomorphic variant of the type 1 Transforming Growth Factor Beta Receptor (TGFBR1), which has been associated with increased cancer risk in some studies. Although TGFBR1*6A is capable of switching TGF-Î² growth inhibitory signals into growth stimulatory signals when stably transfected into MCF-7 breast cancer cells, TGFBR1*6A biological effects are largely unknown. To broadly explore TGFBR1*6A potential oncogenic properties, we assessed its impact on the migration and invasion of MCF-7 cells. We found that TGFBR1*6A significantly enhances MCF-7 cell migration and invasion in a TGF-Î² signaling independent manner. We set up and performed a gene array using the conditions mimicking the cell migration experiments to determine which genes in the migratory pathway were differentially regulated between the MCF-7*6A cells and the MCF-7*9A (wild type transfected) cells. The gene array identified two downregulated genes in *6A compared to *9A that are involved in cell migration and invasion: ARHGAP5, encoding ARHGAP5, and FN1, encoding fibronectin-1 (FN1). We were subsequently able to use this information in further studies in the lab. Experiment Overall Design: MCF-7 cells were stably transfected with pIRES-TGFBR1-HA-FLAG or pIRES-TGFBR1*6A-HA-FLAG. Clones were picked up and named 6A-SA5 and WT-WB1 referring to the *6A and TGFBR1 clones, respectively. We have found that the *6A mutation causes an increase in migration and invasion of MCF-7 cells which is independent of TGF-beta. We used the gene array to identify genes that were differentially regulated between the two cell lines that could lead to this phenotype. We collected RNA from samples that were serum-deprived overnight prior to being fed with complete media to mimic the conditions in the migration experiment. No exogenous growth factors were added to the media besides the normal 10% heat inactivated FBS. Samples were collected and run in triplicate (referred to in this data set as sample 1, sample 2, and sample 3). The âuntreatedâ refers to the fact that samples were grown in complete media alone with no exogenously added growth factors.

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Nudt3 is a mRNA Decapping Enzyme That Modulates Cell Migration

Publications

Nudt3 is an mRNA decapping enzyme that modulates cell migration.

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