The CRISPR-Cas9 crATIC HeLa transcriptome: Characterization of a novel cellular model of ATIC deficiency and ZMP accumulation.

Autor:	Mazzarino RC; Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Avenue, Denver, CO 80210, USA.; Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.; Department of Biological Sciences, University of Denver, Denver, CO 80210, USA.; Molecular and Cellular Biophysics Program, University of Denver, Denver, CO 80210, USA., Baresova V; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Zikánová M; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic., Duval N; Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Avenue, Denver, CO 80210, USA.; Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.; Department of Biological Sciences, University of Denver, Denver, CO 80210, USA., Wilkinson TG 2nd; Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Avenue, Denver, CO 80210, USA.; Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA., Patterson D; Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Avenue, Denver, CO 80210, USA.; Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.; Molecular and Cellular Biophysics Program, University of Denver, Denver, CO 80210, USA., Vacano GN; Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Avenue, Denver, CO 80210, USA.; Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2020 Sep 02; Vol. 25, pp. 100642. Date of Electronic Publication: 2020 Sep 02 (Print Publication: 2020).
DOI:	10.1016/j.ymgmr.2020.100642
Abstrakt:	In de novo purine biosynthesis (DNPS), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (EC 2.1.2.3)/inosine monophosphate cyclohydrolase (EC 3.5.4.10) (ATIC) catalyzes the last two reactions of the pathway: conversion of 5-aminoimidazole-4-carboxamide ribonucleotide [aka Z -nucleotide monophosphate (ZMP)] to 5-formamido-4-imidazolecarboxamide ribonucleotide (FAICAR) then to inosine monophosphate (IMP). Mutations in ATIC cause an untreatable and devastating inborn error of metabolism in humans. ZMP is an adenosine monophosphate (AMP) mimetic and a known activator of AMP-activated protein kinase (AMPK). Recently, a HeLa cell line null mutant for ATIC was constructed via CRISPR-Cas9 mutagenesis. This mutant, crATIC, accumulates ZMP during purine starvation. Given that the mutant can accumulate ZMP in the absence of treatment with exogenous compounds, crATIC is likely an important cellular model of DNPS inactivation and ZMP accumulation. In the current study, we characterize the crATIC transcriptome versus the HeLa transcriptome in purine-supplemented and purine-depleted growth conditions. We report and discuss transcriptome changes with particular relevance to Alzheimer's disease and in genes relevant to lipid and fatty acid synthesis, neurodevelopment, embryogenesis, cell cycle maintenance and progression, extracellular matrix, immune function, TGFβ and other cellular processes. Competing Interests: The authors have no conflicts of interest. (© 2020 The Authors.)
Databáze:	MEDLINE
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