PLoS Genetics最新文献

{"title":"Incomplete paralog compensation generates selective dependency on TRA2A in cancer.","authors":"Amanda R Lee, Anna Tangiyan, Isha Singh, Peter S Choi","doi":"10.1371/journal.pgen.1011685","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011685","url":null,"abstract":"<p><p>Paralogs often exhibit functional redundancy, allowing them to effectively compensate for each other's loss. However, this buffering mechanism is frequently disrupted in cancer, exposing unique paralog-specific vulnerabilities. Here, we identify a selective dependency on the splicing factor TRA2A. We find that TRA2A and its paralog TRA2B are synthetic lethal partners that function as widespread and largely redundant activators of both alternative and constitutive splicing. While loss of TRA2A alone is typically neutral due to compensation by TRA2B, we discover that a subset of cancer cell lines are highly TRA2A-dependent. Upon TRA2A depletion, these cell lines exhibit a lack of paralog buffering specifically on shared splicing targets, leading to defects in mitosis and cell death. Notably, TRA2B overexpression rescues both the aberrant splicing and lethality associated with TRA2A loss, indicating that paralog compensation is dosage-sensitive. Together, these findings reveal a complex dosage-dependent relationship between paralogous splicing factors, and highlight how dysfunctional paralog buffering can create a selective dependency in cancer.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011685"},"PeriodicalIF":4.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An antisense RNA regulates production of DnaA and affects sporulation in Bacillus subtilis.","authors":"Emma L Sedivy, Janet L Smith, Alan D Grossman","doi":"10.1371/journal.pgen.1011625","DOIUrl":"10.1371/journal.pgen.1011625","url":null,"abstract":"<p><p>DnaA is the replication initiator and a transcription factor in virtually all bacteria. Although the synthesis and activity of DnaA are highly regulated, the mechanisms of regulation vary between organisms. We found that production of DnaA in Bacillus subtilis is regulated by an antisense RNA that overlaps with the 5' untranslated region upstream of the dnaA open reading frame. We initially observed this RNA in in vitro transcription experiments and found that its production was inhibited by DnaA. This RNA, now called ArrA for antisense RNA repressor of dnaA, is made in vivo. We identified the arrA promoter and made a mutation that greatly reduced (or eliminated) production of ArrA RNA in vitro and in vivo. In vivo, this arrA promoter mutation caused an increase in the amount of mRNA and protein from dnaA and dnaN, indicating that arrA expression normally inhibits expression of the dnaA-dnaN operon. The arrA mutation also caused a delay in sporulation that was alleviated by loss of sda, a sporulation-inhibitory gene that is directly activated by DnaA. arrA appears to be conserved in some members of the Bacillus genus, indicating that arrA has evolved in at least some endospore-forming bacteria to modulate production of DnaA and enable timely and robust sporulation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011625"},"PeriodicalIF":4.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into region-specific sexual dichromatism: Comparative transcriptome analysis of red cheek pigmentation in zebra finches.","authors":"Gee-Way Lin, Chih-Kuan Chen, Ting-Xin Jiang, Ya-Chen Liang, Pin-Chi Tang, Ping Wu, Randall B Widelitz, Chih-Feng Chen, Cheng-Ming Chuong","doi":"10.1371/journal.pgen.1011693","DOIUrl":"10.1371/journal.pgen.1011693","url":null,"abstract":"<p><p>Feathers, the primary skin appendage covering the avian body, undergo dynamic phenotypic changes throughout a bird's life. Males and females of the same species can exhibit sexually dichromatic plumage colors which play a critical role in mating choice, survival, and ecological interactions. In this study, we investigate the molecular mechanisms underlying the changes of color that occur during the transition from juvenile to adult feathers, known as the secondary transition. We focus on sexual dichromatism of craniofacial plumage and use the male cheek domain of the zebra finch (Taeniopygia guttata) as the major model. The transcriptome of the cheek and scalp (crown) domains in males and females of wild-type and genetic color variants were compared. We found that (1) Craniofacial color patterning operates through two regulatory layers. The first layer involves transcription factor (TF) genes that define the cheek domain such as PITX1, PAX1, PAX6. The second layer comprises pigment-related genes responsible for specific colors, including male-biased TFs (SOX10 and DMRT1) and transporters associated with red pigment synthesis. (2) Surprisingly, ASIP, which controls pheomelanin production in other species, was expressed in both male (red) and female (gray) cheeks. Instead, PAX1 in cheek dermal fibroblasts may serve as an upstream regulator, potentially triggering the male-biased color pattern through PAX6 and SOX10. PAX6 and SOX10 in melanocytes potentially enhance the expression of GPR143, SLC45A2, and TMEM163, driving increased pheomelanin production in males. (3) Sexual dichromatism is associated with sex-linked genes on the Z chromosome, notably SLC45A2. In addition, motif analysis comparing the binding strength between regional transcription factors and melanogenesis genes suggests that craniofacial pigmentation may have evolved convergently in passerine birds. These findings provide novel insights into the molecular control of color patterning and lay the groundwork for further studies on avian sexual dichromatism and secondary feather transition.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011693"},"PeriodicalIF":4.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Heterozygosity associated with ubiquitous environments in yeast.","authors":"Nikilesh Vijayan, Sameer Joshi, Praseetha Sarath, Koodali T Nishant","doi":"10.1371/journal.pgen.1011692","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011692","url":null,"abstract":"<p><p>The effect of ubiquitous environmental conditions on mutational mechanisms, particularly loss of heterozygosity (LOH) remains poorly understood. Environment induced LOH can rapidly alter the genome and promote disease progression. Using mutation accumulation (MA) lines, we analysed the effect of ubiquitous environmental conditions on mutational mechanisms in a diploid hybrid (S288c/YJM789) baker's yeast strain. These included blue light, low glucose (calorie restriction), oxidative stress (H2O2), high temperature (37°C), ethanol, and salt (NaCl). The frequency of LOH increased significantly in all environments including calorie restriction relative to the control (YPD). Interestingly, the percentage of the genome covered by LOH varied significantly depending on the condition. For example, the LOH tracts seen in calorie restriction conditions were significantly shorter than those observed in blue light exposure that rapidly homozygotized the genome. We also report a unique mutational signature of blue light exposure comprising LOH, small indels, large deletions and transversion mutations (G:C > T:A; G:C > C:G), with the latter likely to result from the photooxidation of guanine bases. Our results suggest ubiquitous environmental conditions cause LOH but result in distinct mutational signatures due to the type of damage induced and the pathways used to repair them.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011692"},"PeriodicalIF":4.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordinated transcriptomic and metabolomic responses in rice reveal lignin-based physical barriers as key mechanisms of nonhost resistance to rust fungi.","authors":"Ce Zhang, Liru Jian, Tao Guan, Yiping Wang, Huihui Pang, Yiqian Xu, Yaoyao Xing, Jiawen Wang, Zhensheng Kang, Jing Zhao","doi":"10.1371/journal.pgen.1011679","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011679","url":null,"abstract":"<p><p>Nonhost resistance (NHR) serves as a fundamental defense response in plants against non-adapted pathogens, yet its underlying molecular mechanisms remain poorly understood. This study investigates the rice-Pst (Puccinia striiformis f. sp. tritici) interaction using integrated transcriptomic and metabolomic analyses to unravel the temporal dynamics of gene expression and metabolite changes associated with NHR. Our findings reveal a temporally coordinated activation of defense responses, with early induction of receptor-like kinases (RLKs) and hypersensitive response proteins, followed by later activation of jasmonic acid and systemic acquired resistance pathways, along with the accumulation of amino acids and other phenolic compounds. Notably, metabolic pathways related to cell wall reinforcement were significantly upregulated during Pst infection, highlighted by enhanced lignin biosynthesis (phenylpropanoid pathway), nucleotide sugar metabolism, and tryptophan pathways. Rice mutants deficient in genes involved in lignin biosynthesis (OsPAL3, Os4CL3, Os4CL5, and OsCCoAOMT) displayed reduced lignin deposition at infection sites and compromised resistance to Pst, underscoring a critical role of lignin-based physical barriers in NHR. This study provides novel insights into the molecular framework of rice NHR, emphasizing the pivotal role of structural defenses in plant immunity.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011679"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of eicosanoid signaling in Drosophila development.","authors":"Daiki Fujinaga, Cebrina Nolan, Naoki Yamanaka","doi":"10.1371/journal.pgen.1011705","DOIUrl":"10.1371/journal.pgen.1011705","url":null,"abstract":"<p><p>20-carbon fatty acid-derived eicosanoids are versatile signaling oxylipins in mammals. In particular, a group of eicosanoids termed prostanoids are involved in multiple physiological processes, such as reproduction and immune responses. Although some eicosanoids such as prostaglandin E2 (PGE2) have been detected in some insect species, molecular mechanisms of eicosanoid synthesis and signal transduction in insects have not been thoroughly investigated. Our phylogenetic analysis indicated that, in clear contrast to the presence of numerous receptors for oxylipins and other lipid mediators in humans, the Drosophila genome only possesses a single ortholog of such receptors, which is homologous to human prostanoid receptors. This G protein-coupled receptor, named Prostaglandin Receptor or PGR, is activated by PGE2 and its isomer PGD2 in Drosophila S2 cells. PGR mutant flies die as pharate adults with insufficient tracheal development, which can be rescued by supplying high oxygen. Consistent with this, through a comprehensive mutagenesis approach, we identified a Drosophila PGE synthase whose mutants show similar pharate adult lethality with hypoxia responses. Drosophila thus has a highly simplified eicosanoid signaling pathway as compared to humans, and it may provide an ideal model system for investigating evolutionarily conserved aspects of eicosanoid signaling.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011705"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitin sulfate regulates proliferation of Drosophila intestinal stem cells.","authors":"Collin Knudsen, Ayano Moriya, Eriko Nakato, Rishi Gulati, Takuya Akiyama, Hiroshi Nakato","doi":"10.1371/journal.pgen.1011686","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011686","url":null,"abstract":"<p><p>The basement membrane (BM) plays critical roles in stem cell maintenance and activity control. Here we show that chondroitin sulfate (CS), a major component of the Drosophila midgut BM, is required for proper control of intestinal stem cells (ISCs). Loss of Chsy, a critical CS biosynthetic gene, resulted in elevated levels of ISC proliferation during homeostasis, leading to midgut hyperplasia. Regeneration assays demonstrated that Chsy mutant ISCs failed to properly downregulate mitotic activity at the end of regeneration. We also found that CS is essential for the barrier integrity to prevent leakage of the midgut epithelium. CS is known to be polymerized by the action of the complex of Chsy and another critical protein, Chondroitin polymerizing factor (Chpf). We found that Chpf mutants show increased ISC division during midgut homeostasis and regeneration, similar to Chsy mutants. As Chpf is induced by a tissue damage during regeneration, our data suggest that Chpf functions with Chsy to facilitate CS remodeling and stimulate tissue repair. We propose that the completion of the repair of CS-containing BM acts as a prerequisite to properly terminate the regeneration process.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011686"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fourspine stickleback (Apeltes quadracus) has an XY sex chromosome system with polymorphic inversions on both X and Y chromosomes.","authors":"Zuyao Liu, Amy L Herbert, Yingguang Frank Chan, Marek Kučka, David M Kingsley, Catherine L Peichel","doi":"10.1371/journal.pgen.1011465","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011465","url":null,"abstract":"<p><p>Teleost fish are well-known for possessing a diversity of sex chromosomes and for undergoing frequent turnovers of these sex chromosomes. However, previous studies have mainly focused on variation between species, while comparatively little attention has been given to sex chromosome polymorphisms within species, which may capture early stages of sex chromosome changes. To better understand the evolution of sex chromosomes, we used the fourspine stickleback (Apeltes quadracus) as a model organism. Previous cytogenetic studies suggested that females of this species possessed a ZW heteromorphic sex chromosome system. However, genetic crosses and our whole-genome sequencing of three geographically distinct wild populations revealed that A. quadracus has an XY sex chromosome on chromosome 23. This chromosome has not previously been identified as a sex chromosome in any other stickleback species, indicating a recent sex chromosome turnover. We also identified two genes - rxfp2a and zar1l - as novel candidate sex determination genes. Notably, we observed inversions on both the X and Y chromosomes in different populations, resulting in distinctive patterns of differentiation between the X and Y chromosomes across populations. The new sex chromosome and intraspecies inversion polymorphisms observed in A. quadracus provide an excellent system for future work assessing the relative fitness effects of the inversions, which will enable testing theoretical models about the drivers of sex chromosome evolution and turnover.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011465"},"PeriodicalIF":4.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.","authors":"Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim","doi":"10.1371/journal.pgen.1011700","DOIUrl":"10.1371/journal.pgen.1011700","url":null,"abstract":"<p><p>Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and improving the ER's ability to handle proteostasis. MERSR activation in both polyglutamine and amyloid-beta peptide-expressing C. elegans disease models also led to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011700"},"PeriodicalIF":4.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel male accessory gland peptide reduces female post-mating receptivity in the brown planthopper.","authors":"Yi-Jie Zhang, Ning Zhang, Ruo-Tong Bu, Dick R Nässel, Cong-Fen Gao, Shun-Fan Wu","doi":"10.1371/journal.pgen.1011699","DOIUrl":"10.1371/journal.pgen.1011699","url":null,"abstract":"<p><p>Mating in insects commonly induces a profound change in the physiology and behavior of the female that serves to secure numerous and viable offspring, and to ensure paternity for the male by reducing receptivity of the female to further mating attempts. Here, we set out to characterize the post-mating response (PMR) in a pest insect, the brown planthopper Nilaparvata lugens and to identify a functional analog of sex peptide and/or other seminal fluid factors that contribute to the PMR in Drosophila. We find that N. lugens display a distinct PMR that lasts for about 4 days and includes a change in female behavior with decreased receptivity to males and increased oviposition. Extract from male accessory glands (MAG) injected into virgin females triggers a similar PMR, lasting about 24h. Since sex peptide does not exist in N. lugens, we screened for candidate mediators by performing a transcriptional and proteomics analysis of MAG extract. We identified a novel 51 amino acid peptide present only in the MAG and not in female N. lugens. This peptide, that we designate maccessin (macc), affects the female PMR. Females mated by males with macc knockdown display receptivity to wild type males in a second mating, which does not occur in controls. However, oviposition is not affected. Injection of recombinant macc reduces female receptivity, with no effect on oviposition. Thus, macc is an important seminal fluid peptide that affects the PMR of N. lugens. Our analysis suggests that the gene encoding the macc precursor is restricted to species closely related to N. lugens.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 5","pages":"e1011699"},"PeriodicalIF":4.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}