title: APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo.
abstract: Editing of the human and murineApoBmRNA by APOBEC1, the catalytic enzyme of the protein complex that catalyzes C-to-U RNA editing, creates an internal stop codon within the APOB coding sequence, generating two protein isoforms. It has been long held that APOBEC1-mediated editing activity is dependent on the RNA binding protein A1CF. The function of A1CF in adult tissues has not been reported because a previously reported null allele displays embryonic lethality. This work aimed to address the function of A1CF in adult mouse tissues using a conditionalA1cfallele. Unexpectedly,A1cf-null mice were viable and fertile with modest defects in hematopoietic, immune, and metabolic parameters. C-to-U RNA editing was quantified for multiple targets, includingApoB, in the small intestine and liver. In all cases, no changes in RNA editing efficiency were observed. Blood plasma analysis demonstrated a male-specific increase in solute concentration and increased cellularity in the glomeruli of maleA1cf-null mice. Urine analysis showed a reduction in solute concentration, suggesting abnormal water homeostasis and possible kidney abnormalities exclusive to the male. Computational identification of kidney C-to-U editing sites from polyadenylated RNA-sequencing identified a number of editing sites exclusive to the kidney. However, molecular analysis of kidney C-to-U editing showed no changes in editing efficiency with A1CF loss. Taken together, these observations demonstrate that A1CF does not act as the APOBEC1 complementation factor in vivo under normal physiological conditions and suggests new roles for A1CF, specifically within the male adult kidney.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Snyder
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: McCarty
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Mehalow
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Svenson
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Murray
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Braun
mesh_terms: D000071479:APOBEC-1 Deaminase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D005260:Female; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000172:deficiency / Q000235:genetics*; D007421:Intestine, Small / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D014883:Water-Electrolyte Imbalance
chemical_list: D001055:Apolipoproteins B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C503503:apobec-1 complementation factor, mouse; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse
keywords: ACF; APOB; APOBEC1; RNA editing; kidney