Expression, not sequence, distinguishes miR-238 from its miR-239ab sister miRNAs in promoting longevity in < i > Caenorhabditis elegans < /i >
We present evidence that the lack of redundancy betweenmiR-238 andmiR-239ab is independent of their sequence differences; miR-239a or miR-239b could substitute for the longevity role of miR-238 when expressed from themiR-238 locus. Altogether, these studies disqualify miR-239ab as negative regulators of aging and demonstrate that expression, not sequence, dictates the specific role of miR-238 in promoting longevity. (Source: PLoS Genetics)
Source: PLoS Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Laura B. Chipman Source Type: research
Accurate phenotypic classification and exome sequencing allow identification of novel genes and variants associated with adult-onset hearing loss
by Morag A. Lewis, Jennifer Schulte, Lois Matthews, Kenneth I. Vaden Jr., Claire J Steves, Frances M. K. Williams, Bradley A. Schulte, Judy R. Dubno, Karen P. Steel
Adult-onset progressive hearing loss is a common, complex disease with a strong genetic component. Although to date over 150 genes have been identified as contributing to human hearing loss, many more remain to be discovered, as does most of the underlying genetic diversity. Many different variants have been found to underlie adult-onset hearing loss, but they tend to be rare variants with a high impact upon the gene product. It is likely that combinations of ...
Source: PLoS Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Morag A. Lewis Source Type: research
Efficient sex separation by exploiting differential alternative splicing of a dominant marker in < i > Aedes aegypti < /i >
by Shih-Che Weng, Igor Antoshechkin, Eric Marois, Omar S. Akbari
Only female mosquitoes consume blood giving them the opportunity to transmit deadly human pathogens. Therefore, it is critical to remove females before conducting releases for genetic biocontrol interventions. Here we describe a robust sex-sorting approach termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter) that exploits sex-specific alternative splicing of an innocuous reporter to ensure exclusive dominant male-specific expression. Using SEPARATOR, we demonstrate reliable sex selection from early larval...
Source: PLoS Genetics - November 27, 2023 Category: Genetics & Stem Cells Authors: Shih-Che Weng Source Type: research
Phosphorylation of AHR by PLK1 promotes metastasis of LUAD via DIO2-TH signaling
In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses reveal that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), activating thyroid hormone (TH) signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or a deiodinase inhibitor disrupts this property. Taking together, our results identify the AHR phosphorylation by PLK1 and subs...
Source: PLoS Genetics - November 21, 2023 Category: Genetics & Stem Cells Authors: Chaohao Li Source Type: research
ZmEREB92 plays a negative role in seed germination by regulating ethylene signaling and starch mobilization in maize
by Jingye Fu, Wenzheng Pei, Linqian He, Ben Ma, Chen Tang, Li Zhu, Liping Wang, Yuanyuan Zhong, Gang Chen, Qi Wang, Qiang Wang
Rapid and uniform seed germination is required for modern cropping system. Thus, it is important to optimize germination performance through breeding strategies in maize, in which identification for key regulators is needed. Here, we characterized an AP2/ERF transcription factor, ZmEREB92, as a negative regulator of seed germination in maize. Enhanced germination inereb92 mutants is contributed by elevated ethylene signaling and starch degradation. Consistently, an ethylene signaling geneZmEIL7 an...
Source: PLoS Genetics - November 17, 2023 Category: Genetics & Stem Cells Authors: Jingye Fu Source Type: research
XRE transcription factors conserved in < i > Caulobacter < /i > and φCbK modulate adhesin development and phage production
by Maeve McLaughlin, Aretha Fiebig, Sean Crosson
The xenobiotic response element (XRE) family of transcription factors (TFs), which are commonly encoded by bacteria and bacteriophage, regulate diverse features of bacterial cell physiology and impact phage infection dynamics. Through a pangenome analysis ofCaulobacter species isolated from soil and aquatic ecosystems, we uncovered an apparent radiation of a paralogous XRE TF gene cluster, several of which have established functions in the regulation of holdfast adhesin development and biofilm formation inC.crescentus. We further discovered related XRE TFs throughout the cl...
Source: PLoS Genetics - November 16, 2023 Category: Genetics & Stem Cells Authors: Maeve McLaughlin Source Type: research
The activity of < i > engrailed < /i > imaginal disc enhancers is modulated epigenetically by chromatin and autoregulation
by Yuzhong Cheng, Fountane Chan, Judith A. Kassisengrailed (en) encodes a homeodomain transcription factor crucial for the proper development of Drosophila embryos and adults. Like many developmental transcription factors,en expression is regulated by many enhancers, some of overlapping function, that drive expression in spatially and temporally restricted patterns. Theen embryonic enhancers are located in discrete DNA fragments that can function correctly in small reporter transgenes. In contrast, theen imaginal disc enhancers (IDEs) do not function correctly in small reporter transgenes. En is expressed in the posterior ...
Source: PLoS Genetics - November 15, 2023 Category: Genetics & Stem Cells Authors: Yuzhong Cheng Source Type: research
Correction: The circadian clock gene < i > bmal1 < /i > is necessary for co-ordinated circatidal rhythms in the marine isopod < i > Eurydice pulchra < /i > (Leach)
by Lin Zhang, Edward W. Green, Simon G. Webster, Michael H. Hastings, David C. Wilcockson, Charalambos P. Kyriacou (Source: PLoS Genetics)
Source: PLoS Genetics - November 15, 2023 Category: Genetics & Stem Cells Authors: Lin Zhang Source Type: research
Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D
by Xiaotong Wang, Valentin Hivert, Shiane Groot, Ying Wang, Loic Yengo, John J. McGrath, Kathryn E. Kemper, Peter M. Visscher, Naomi R. Wray, Joana A. Revez
Vitamin D status –a complex trait influenced by environmental and genetic factors–is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)–the main circulating form of vitamin D–in...
Source: PLoS Genetics - November 14, 2023 Category: Genetics & Stem Cells Authors: Xiaotong Wang Source Type: research
MIWI N-terminal RG motif promotes efficient pachytene piRNA production and spermatogenesis independent of LINE1 transposon silencing
by Chao Wei, Jiongjie Jing, Xiaoyuan Yan, Jeffrey M. Mann, Ruirong Geng, Huirong Xie, Elena Y. Demireva, Rex A. Hess, Deqiang Ding, Chen Chen
PIWI proteins and their associated piRNAs act to silence transposons and promote gametogenesis. Murine PIWI proteins MIWI, MILI, and MIWI2 have multiple arginine and glycine (RG)-rich motifs at their N-terminal domains. Despite being known as docking sites for the TDRD family proteins, thein vivo regulatory roles for these RG motifs in directing PIWI in piRNA biogenesis and spermatogenesis remain elusive. To investigate the functional significance of RG motifs in mammalian PIWI prot...
Source: PLoS Genetics - November 13, 2023 Category: Genetics & Stem Cells Authors: Chao Wei Source Type: research
Correction: Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
by David Melamed, Aaron Choi, Amy Reilein, Simon Tavar é, Daniel Kalderon (Source: PLoS Genetics)
Source: PLoS Genetics - November 13, 2023 Category: Genetics & Stem Cells Authors: David Melamed Source Type: research
Checkpoint phosphorylation sites on budding yeast Rif1 protect nascent DNA from degradation by Sgs1-Dna2
by Vamsi Krishna Gali, Chandre Monerawela, Yassine Laksir, Shin-ichiro Hiraga, Anne D. Donaldson
In budding yeast the Rif1 protein is important for protecting nascent DNA at blocked replication forks, but the mechanism has been unclear. Here we show that budding yeast Rif1 must interact with Protein Phosphatase 1 to protect nascent DNA. In the absence of Rif1, removal of either Dna2 or Sgs1 prevents nascent DNA degradation, implying that Rif1 protects nascent DNA by targeting Protein Phosphatase 1 to oppose degradation by the Sgs1-Dna2 nuclease-helicase complex. This functional role for Rif1 is conserved from yeast to hum...
Source: PLoS Genetics - November 13, 2023 Category: Genetics & Stem Cells Authors: Vamsi Krishna Gali Source Type: research
Genome mining yields putative disease-associated ROMK variants with distinct defects
by Nga H. Nguyen, Srikant Sarangi, Erin M. McChesney, Shaohu Sheng, Jacob D. Durrant, Aidan W. Porter, Thomas R. Kleyman, Zachary W. Pitluk, Jeffrey L. Brodsky
Bartter syndrome is a group of rare genetic disorders that compromise kidney function by impairing electrolyte reabsorption. Left untreated, the resulting hyponatremia, hypokalemia, and dehydration can be fatal, and there is currently no cure. Bartter syndrome type II specifically arises from mutations inKCNJ1, which encodes the renal outer medullary potassium channel, ROMK. Over 40 Bartter syndrome-associated mutations inKCNJ1 have been identified, yet their molec...
Source: PLoS Genetics - November 13, 2023 Category: Genetics & Stem Cells Authors: Nga H. Nguyen Source Type: research
Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis
by Esther Herruzo, Estefan ía Sánchez-Díaz, Sara González-Arranz, Beatriz Santos, Jesús A. Carballo, Pedro A. San-Segundo
The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads t...
Source: PLoS Genetics - November 10, 2023 Category: Genetics & Stem Cells Authors: Esther Herruzo Source Type: research
< i > RET < /i > enhancer haplotype-dependent remodeling of the human fetal gut development program
by Sumantra Chatterjee, Lauren E. Fries, Or Yaacov, Nan Hu, Hanna E. Berk-Rauch, Aravinda Chakravarti
Hirschsprung disease (HSCR) is associated with deficiency of the receptor tyrosine kinase RET, resulting in loss of cells of the enteric nervous system (ENS) during fetal gut development. The major contribution to HSCR risk is from common sequence variants inRET enhancers with additional risk from rare coding variants in many genes. Here, we demonstrate that theseRET enhancer variants specifically alter the human fetal gut development program through significant decreases in gene expression ofRET, members of theRET-EDNRB ...
Source: PLoS Genetics - November 10, 2023 Category: Genetics & Stem Cells Authors: Sumantra Chatterjee Source Type: research
