Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias

Carouge, Delphine; Blanc, Valérie; Knoblaugh, Sue E.; Hunter, Robert J.; Davidson, Nicholas O.; Nadeau, Joseph H.

doi:10.1073/pnas.1604773113

Cited by 21 publications

(25 citation statements)

References 137 publications

(192 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Firstly, the embryonic lethality reported for A1cf tm1Ddsn occurs early in gestation, between E3.5 and E7.5, and prior to the reported onset of A1cf expression (Blanc et al 2005). Secondly, a recent report demonstrated that the A1cf tm1Ddsn allele displays a transmission distortion ratio (Carouge et al 2016), which is often indicative of chromosomal rearrangements such as Robertsonian translocations (Underkoffler et al 2005). Taken together, this evidence suggests the A1cf tm1Ddsn allele phenotype may be a result of additional, unintended genetic alterations unrelated to the loss of A1CF.…”

Section: Discussionmentioning

confidence: 99%

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

Snyder

McCarty

Mehalow

et al. 2017

RNA

View full text Add to dashboard Cite

Editing of the human and murine ApoB mRNA 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 conditional A1cf allele. 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, including ApoB, 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 male A1cf-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.

show abstract

Section: Discussionmentioning

confidence: 99%

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

Snyder

McCarty

Mehalow

et al. 2017

RNA

View full text Add to dashboard Cite

show abstract

“…For Pum1, m/m embryos were not detected at E3.5 and litter size did not differ between intercrosses and backcrosses. 47 For A1cf, the heterozygote excess ranges from 3-to 5-fold, instead of the expected value of 2, based on two reports; 48,49 Loss of homozygous embryos between E3.5 -4.5 does not account for excess heterozygosity or for normal litter size. 48 Although litter size was not reported for Ppp2cb, 50 the highly significant heterozygote excess (>3:1) in intercrosses versus backcrosses is striking and consistent with results for A1cf, Ddx1 (see below) and Pum1.…”

Section: What Is the Evidence For Fertilization Bias?mentioning

confidence: 99%

“…[188][189][190] Various mechanisms preserve genomic integrity and developmental capacity of the 'mother of all stem cell lineages' 191 by repairing DNA defects, 192 maintaining cellular conditions, 193 suppressing transposon activity, [194][195][196][197][198][199] and programming epigenetic state. 200,201 Failure of pluripotency control can lead to precocious differentiation of germ cells, 202,203 spontaneous transformation of germ cells during fetal development, 142,185,186,204 , infertility, 49,205,206 and other reproductive disorders. 204 Dysfunction can also lead to inherited epigenetic changes that affect risk for TGCTs and urogenital abnormalities in offspring and later generations in the absence of genes that originally triggered these transgenerational effects.…”

Section: What Are the Mechanisms?mentioning

confidence: 99%

“…204 Dysfunction can also lead to inherited epigenetic changes that affect risk for TGCTs and urogenital abnormalities in offspring and later generations in the absence of genes that originally triggered these transgenerational effects. 49,59,182,183 Genetic anomalies together with dietary, hormonal and other environmental influences may induce germline dysfunctions that manifest as conventional genetic effects, unconventional epigenetic inheritance, and now preference for particular gamete combinations at fertilization. 49,59,74 Perspectives Given this evidence, how might biased fertilization work?…”

Section: What Are the Mechanisms?mentioning

confidence: 99%

“…49,59,182,183 Genetic anomalies together with dietary, hormonal and other environmental influences may induce germline dysfunctions that manifest as conventional genetic effects, unconventional epigenetic inheritance, and now preference for particular gamete combinations at fertilization. 49,59,74 Perspectives Given this evidence, how might biased fertilization work? We can identify essential elements and conditions, but we can be less certain about the ways that these genes affect fertilization.Two components are needed for bias, one in females, the other in males; neither alone is sufficient.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Do gametes woo? Evidence for non-random unions at fertilization

Nadeau

2017

Preprint

Self Cite

View full text Add to dashboard Cite

A fundamental tenet of inheritance in sexually reproducing organisms such as humans and laboratory mice is that genetic variants combine randomly at fertilization, thereby ensuring a balanced and statistically predictable representation of inherited variants in each generation. This principle is encapsulated in Mendel's First Law. But exceptions are known. With transmission ratio distortion (TRD), particular alleles are preferentially transmitted to offspring without reducing reproductive productivity. Preferential transmission usually occurs in one sex but not both and is not known to require interactions between gametes at fertilization. We recently discovered, in our work in mice and in other reports in the literature, instances where any of 12 mutant genes bias fertilization, with either too many or too few heterozygotes and too few homozygotes, depending on the mutant gene and on dietary conditions. Although such deviations are usually attributed to embryonic lethality of the under-represented genotypes, the evidence is more consistent with genetically-determined preferences for specific combinations of egg and sperm at fertilization that results in genotype bias without embryo loss. These genes and diets could bias fertilization in at least three not mutually exclusive ways. They could trigger a reversal in the order of meiotic divisions during oogenesis so that the genetics of fertilizing sperm elicits preferential chromatid segregation, thereby dictating which allele remains in the egg versus the 2 nd polar body. Bias could also result from genetic-and diet-induced anomalies in polyamine metabolism on which function of haploid gametes normally depends. Finally, secreted and cell-surface factors in female reproductive organs could control access of sperm to eggs based on their genetic content. This unexpected discovery of genetically-biased fertilization in mice could yield insights about the molecular and cellular interactions between sperm and egg at fertilization, with implications for our understanding of inheritance, reproduction, population genetics, and medical genetics. [298 words]All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/127134 doi: bioRxiv preprint first posted online Apr. 13, 2017; 3 Our understanding of inheritance in sexually reproducing organisms assumes, with good evidence, that the combination of egg and sperm at fertilization is largely independent of their genetic content. This equal transmission of alternative alleles through meiosis in heterozygotes ensures a balanced parental genetic contribution to offspring at each generation. Mendel's First Law captures this principle, which is one of the few that applies generally in biology. Independent segregation and random union of gametes at fertilization are foundations of classical, quantitative, population, evolutionary and me...

show abstract

The selfish environment meets the selfish gene: Coevolution and inheritance of RNA and DNA pools

Monaco

2022

BioEssays

View full text Add to dashboard Cite

Throughout evolution, there has been interaction and exchange between RNA pools in the environment, and DNA and RNA pools of eukaryotic organisms. Metagenomic and metatranscriptomic sequencing of invertebrate hosts and their microbiota has revealed a rich evolutionary history of RNA virus shuttling between species. Horizontal transfer adapted the RNA pool for successful future interactions which lead to zoonotic transmission and detrimental RNA viral pandemics like SARS‐CoV2. In eukaryotes, noncoding RNA (ncRNA) is an established mechanism derived from prokaryotes to defend against viral attack through innate immunity and regulation of host‐derived mRNA. Transgenerational inheritance of ncRNA is evidence for feedforward adaptive immunity and epigenetically encoded environmental change across generations, which may explain the ‘‘missing heritability’’ of common disease. Causal graph theory and the Price Equation can model epigenetic inheritance involving dynamic internal and external RNA pools. Experimental designs should include metatranscriptomic analyses to understand how ncRNA responds to rapidly changing environmental conditions, within and between organisms, and across generations.

show abstract

Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias

Cited by 21 publications

References 137 publications

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo

Do gametes woo? Evidence for non-random unions at fertilization

The selfish environment meets the selfish gene: Coevolution and inheritance of RNA and DNA pools

Contact Info

Product

Resources

About