Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts

Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts Publisher Pubmed

Niavarani A^{1, 2} ; Currie E¹ ; Reyal Y³ ; Anjosafonso F¹ ; Horswell S⁴ ; Griessinger E⁵ ; Sardina JL⁶ ; Bonnet D¹

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1. Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom
2. Digestive Disease Research Institute (DDRI), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Haematology, University College London Hospitals NHS Trust, London, United Kingdom
4. Department of Bioinformatics, Cancer Research UK, London Research Institute, London, United Kingdom
5. INSERM U1065, Mediterranean Centre for Molecular Medicine (C3M), Universite Nice Sophia Antipolis, Nice, France
6. Instituto de Biologia Funcional y Genomica, CSIC, Universidad de Salamanca, Salamanca, Spain

Source: PLoS ONE Published:2015

Abstract

Classic deamination mRNA changes, including cytidine to uridine (C-to-U) and adenosine to inosine (A-to-I), are important exceptions to the central dogma and lead to significant alterations in gene transcripts and products. Although there are a few reports of non-classic mRNA alterations, as yet there is no molecular explanation for these alternative changes. Wilms Tumor 1 (WT1) mutations and variants are implicated in several diseases, including Wilms tumor and acute myeloid leukemia (AML). We observed two alternative G-to-A changes, namely c.1303G>A and c.1586G>A in cDNA clones and found them to be recurrent in a series of 21 umbilical cord blood mononuclear cell (CBMC) samples studied. Two less conserved U-to-C changes were also observed. These alternative changes were found to be significantly higher in non-progenitor as compared to progenitor CBMCs, while they were found to be absent in a series of AML samples studied, indicating they are targeted, cell type-specific mRNA editing modifications. Since APOBEC/ADAR family members are implicated in RNA/DNA editing, we screened them by RNA-interference (RNAi) for WT1-mRNA changes and observed near complete reversal of WT1 c.1303G>A alteration upon APOBEC3A (A3A) knockdown. The role of A3A in mediating this change was confirmed by A3A overexpression in Fujioka cells, which led to a significant increase in WT1 c.1303G>A mRNA editing. Non-progenitor CBMCs showed correspondingly higher levels of A3A-mRNA and protein as compared to the progenitor ones. To our knowledge, this is the first report of mRNA modifying activity for an APOBEC3 protein and implicates A3A in a novel G-to-A form of editing. These findings open the way to further investigations into the mechanisms of other potential mRNA changes, which will help to redefine the RNA editing paradigm in both health and disease. © 2015 Niavarani et al.

2. Pancancer Analysis Identifies Prognostic High-Apobec1 Expression Level Implicated in Cancer In-Frame Insertions and Deletions, Carcinogenesis (2018)

3. The Wilms Tumor-1 (Wt1) Rs2234593 Variant Is a Prognostic Factor in Normal Karyotype Acute Myeloid Leukemia, Annals of Hematology (2016)

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Ahmadreza Niavarani (3)

Style	Citing Format
MLA	Niavarani A, et al.. "Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts." PLoS ONE, vol. 10, no. 3, 2015, pp. -.
APA	Niavarani A, Currie E, Reyal Y, Anjosafonso F, Horswell S, Griessinger E, Sardina JL, Bonnet D (2015). Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts. PLoS ONE, 10(3), -.
Chicago	Niavarani A, Currie E, Reyal Y, Anjosafonso F, Horswell S, Griessinger E, Sardina JL, Bonnet D. "Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts." PLoS ONE 10, no. 3 (2015): -.
Harvard	Niavarani A et al. (2015) 'Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts', PLoS ONE, 10(3), pp. -.
Vancouver	Niavarani A, Currie E, Reyal Y, Anjosafonso F, Horswell S, Griessinger E, et al.. Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts. PLoS ONE. 2015;10(3):-.
BibTex	@article{ author = {Niavarani A and Currie E and Reyal Y and Anjosafonso F and Horswell S and Griessinger E and Sardina JL and Bonnet D}, title = {Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts}, journal = {PLoS ONE}, volume = {10}, number = {3}, pages = {-}, year = {2015} }
RIS	TY - JOUR AU - Niavarani A AU - Currie E AU - Reyal Y AU - Anjosafonso F AU - Horswell S AU - Griessinger E AU - Sardina JL AU - Bonnet D TI - Apobec3a Is Implicated in a Novel Class of G-To-A Mrna Editing in Wt1 Transcripts JO - PLoS ONE VL - 10 IS - 3 SP - EP - PY - 2015 ER -

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