Emerging roles for nucleoporins in reproductive cellular physiology

Preston, Claudia C.; Storm, Emily C.; Leonard, Riley J; Faustino, Randolph S.

doi:10.1139/cjpp-2018-0436

Cited by 5 publications

(6 citation statements)

References 59 publications

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“…In addition, sex-dependent skewing is observed for multiple variants, e.g., V402M, I553M, G754R, D429V, R750H, and R336H (Figure 2) that may indicate a sexassociated predilection for expression of these NUP155 variants. Indeed, gonadal enrichment of specific nup isoforms has been reported (34,35), however the effects of a non-normal population distribution cannot be ruled out in the present study.…”

Section: Discussionmentioning

confidence: 55%

Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot

Leonard

Preston

Gucwa

et al. 2020

Front. Cardiovasc. Med.

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Functional variants in nuclear envelope genes are implicated as underlying causes of cardiopathology. To examine the potential association of single nucleotide variants of nucleoporin genes with cardiac disease, we employed a prognostic scoring approach to investigate variants of NUP155, a nucleoporin gene clinically linked with atrial fibrillation. Here we implemented bioinformatic profiling and predictive scoring, based on the gnomAD, National Heart Lung and Blood Institute-Exome Sequencing Project (NHLBI-ESP) Exome Variant Server, and dbNSFP databases to identify rare single nucleotide variants (SNVs) of NUP155 potentially associated with cardiopathology. This predictive scoring revealed 24 SNVs of NUP155 as potentially cardiopathogenic variants located primarily in the N-terminal crescent-shaped domain of NUP155. In addition, a predicted NUP155 R672G variant prioritized in our study was mapped to a region within the alpha helical stack of the crescent domain of NUP155. Bioinformatic analysis of inferred protein-protein interactions of NUP155 revealed over representation of top functions related to molecular transport, RNA trafficking, and RNA post-transcriptional modification. Topology analysis revealed prioritized hubs critical for maintaining network integrity and informational flow that included FN1, SIRT7, and CUL7 with nodal enrichment of RNA helicases in the topmost enriched subnetwork. Furthermore, integration of the top 5 subnetworks to capture network topology of an expanded framework revealed that FN1 maintained its hub status, with elevation of EED, CUL3, and EFTUD2. This is the first study to report novel discovery of a NUP155 subdomain hotspot that enriches for allelic variants of NUP155 predicted to be clinically damaging, and supports a role for RNA metabolism in cardiac disease and development.

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Section: Discussionmentioning

confidence: 55%

Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot

Leonard

Preston

Gucwa

et al. 2020

Front. Cardiovasc. Med.

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“…Moreover, we are aware that there are substantial differences in mammalian and Drosophila oogenesis. This includes the time at which follicles are created during the life cycle, as well as factors that control oocyte maturation such as the respective hormones involved 99–102 . Nonetheless, we are positive that our investigations are directional towards a better understanding of the putative role of lithium in female fecundity and its potential molecular targets.…”

Section: Discussionmentioning

confidence: 93%

“…This includes the time at which follicles are created during the life cycle, as well as factors that control oocyte maturation such as the respective hormones involved. [99][100][101][102] Nonetheless, we are positive that our investigations are directional towards a better understanding of the putative role of lithium in female fecundity and its potential molecular targets. According to the most recent literature, it is evident that lithium affects the activities and fate of mammalian stem cells and that this trace element is also capable of stimulating the maturation of murine and human primordial oocytes.…”

Section: Discussionmentioning

confidence: 95%

Dietary lithium stimulates female fecundity in Drosophila melanogaster

Jans,

Lüersen,

von Frieling

et al. 2023

BioFactors

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The trace element lithium exerts a versatile bioactivity in humans, to some extend overlapping with in vivo findings in the model organism Drosophila melanogaster. A potentially essential function of lithium in reproduction has been suggested since the 1980s and multiple studies have since been published postulating a regulatory role of lithium in female gametogenesis. However, the impact of lithium on fruit fly egg production has not been at the center of attention to date. In the present study, we report that dietary lithium (0.1–5.0 mM LiCl) substantially improved life time egg production in D. melanogaster w1118 females, with a maximum increase of plus 45% when supplementing 1.0 mM LiCl. This phenomenon was not observed in the insulin receptor mutant InRE19, indicating a potential involvement of insulin‐like signaling in the lithium‐mediated fecundity boost. Analysis of the whole‐body and ovarian transcriptome revealed that dietary lithium affects the mRNA levels of genes encoding proteins related to processes of follicular maturation. To the best of our knowledge, this is the first report on dietary lithium acting as an in vivo fecundity stimulant in D. melanogaster, further supporting the suggested benefit of the trace element in female reproduction.

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“…Other genes associated with our outlier SNPs are Aladin and Rngo . Aladin is a component of the nuclear pore complex, and mutants in this gene are hypersensitive to oxidative stress with decreased ability for DNA repair (Preston et al, 2019 ). Rngo (rings lost), a homolog of human Ddi1 (DNA‐damage inducible protein 1), encodes a conserved ubiquitin receptor which plays a role in shuttling proteins for degradation.…”

Section: Discussionmentioning

confidence: 99%

Section: Genomic Patternsmentioning

confidence: 99%

The genetic basis and adult reproductive consequences of developmental thermal plasticity

Rodrigues

Zwoinska

Wiberg

et al. 2022

Journal of Animal Ecology

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Increasing temperature and thermal variability generate profound selection on populations. Given the fast rate of environmental change, understanding the role of plasticity and genetic adaptation in response to increasing temperatures is critical. This may be especially true for thermal effects on reproductive traits in which thermal fertility limits at high temperatures may be lower than for survival traits. Consequences of changing environments during development on adult phenotypes may be particularly problematic for core traits such as reproduction that begin early in development. Here we examine the consequences of developmental thermal plasticity on subsequent adult reproductive traits and its genetic basis. We used a panel of Drosophila melanogaster (the Drosophila Genetic Reference Panel; DGRP) in which male fertility performance was previously defined as either showing relatively little (status = ‘high’‐performing lines) or substantial (‘low’‐performing lines) decline when exposed to increasing developmental temperatures. We used a thermal reaction norm approach to quantify variation in the consequences of developmental thermal plasticity on multiple adult reproductive traits, including sex‐specific responses, and to identify candidate genes underlying such variation. Developmental thermal stress impacted the means and thermal reaction norms of all reproductive traits except offspring sex ratio. Mating success declined as temperature increased with no difference between high and low lines, whereas increasing temperature resulted in declines for both male and female fertility and productivity but depended on line status. Fertility and offspring number were positively correlated within and between the sexes across lines, but males were more affected than females. We identified 933 SNPs with significant evolved genetic differentiation between high and low lines. In all, 54 of these lie within genomic windows of overall high differentiation, have significant effects of genotype on the male thermal reaction norm for productivity and are associated with 16 genes enriched for phenotypes affecting reproduction, stress responses and autophagy in Drosophila and other organisms. Our results illustrate considerable plasticity in male thermal limits on several reproductive traits following development at high temperature, and we identify differentiated loci with relevant phenotypic effects that may contribute to this population variation. While our work is on a single population, phenotypic results align with an increasing number of studies demonstrating the potential for stronger selection of thermal stress on reproductive traits, particularly in males. Such large fitness costs may have both short‐ and long‐term consequences for the evolution of populations in response to a warming world.

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Emerging roles for nucleoporins in reproductive cellular physiology

Cited by 5 publications

References 59 publications

Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot

Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot

Dietary lithium stimulates female fecundity in Drosophila melanogaster

The genetic basis and adult reproductive consequences of developmental thermal plasticity

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