PLoS Genetics最新文献

{"title":"Correction: Reduced crossover interference and increased ZMM-independent recombination in the absence of Tel1/ATM.","authors":"Carol M Anderson, Ashwini Oke, Phoebe Yam, Tangna Zhuge, Jennifer C Fung","doi":"10.1371/journal.pgen.1011779","DOIUrl":"10.1371/journal.pgen.1011779","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1005478.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011779"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585452","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":"Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.","authors":"Leonor Miller-Fleming, Wing Hei Au, Laura Raik, Pedro Rebelo-Guiomar, Jasper Schmitz, Ha Yoon Cho, Aron Czako, Alexander J Whitworth","doi":"10.1371/journal.pgen.1011773","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011773","url":null,"abstract":"<p><p>Mitochondria perform essential metabolic functions and respond rapidly to changes in metabolic and stress conditions. As the majority of mitochondrial proteins are nuclear-encoded, intricate post-transcriptional regulation is crucial to enable mitochondria to adapt to changing cellular demands. The eukaryotic Clustered mitochondria protein family has emerged as an important regulator of mitochondrial function during metabolic shifts. Here, we show that the Drosophila melanogaster and Saccharomyces cerevisiae Clu/Clu1 proteins form dynamic, membraneless, mRNA-containing granules adjacent to mitochondria in response to metabolic changes. Yeast Clu1 regulates the translation of a subset of nuclear-encoded mitochondrial proteins by interacting with their mRNAs while these are engaged in translation. We further show that Clu1 regulates translation by interacting with polysomes, independently of whether it is in a diffuse or granular state. Our results demonstrate remarkable functional conservation with other members of the Clustered mitochondria protein family and suggest that Clu/Clu1 granules isolate and concentrate ribosomes engaged in translating their mRNA targets, thus, integrating metabolic signals with the regulation of mitochondrial protein synthesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011773"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585451","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":"SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.","authors":"Danae Morales Angeles, Kaitlyn Coleman, Chimezie Progress Odika, Chris L B Graham, Helena Chan, Michael Gilmore, Najwa Taib, Elda Bauda, Christine Moriscot, Benoit Gallet, Hannah Fisher, Per A Bullough, Cécile Morlot, Darius Köster, Simonetta Gribaldo, Felipe Cava, Christopher D A Rodrigues","doi":"10.1371/journal.pgen.1011768","DOIUrl":"10.1371/journal.pgen.1011768","url":null,"abstract":"<p><p>During endospore formation, the mother cell and developing spore establish cell-cell signalling pathways that lead to compartment-specific transcription and key steps in morphogenesis. Endospore-forming bacteria also assemble a highly conserved essential membrane complex, called the A-Q complex, that physically connects these cells and may serve as a molecular conduit between them. While SpoIIIL was previously identified as a putative A-Q complex component in Bacillus subtilis, its exact role remains unclear. Here, we found that SpoIIIL does not function in the A-Q complex but instead acts as a forespore-specific factor required for efficient cell-cell signalling that leads to late mother cell transcription. Quantitative image analysis revealed that spoIIIL mutant spores do not exhibit hallmark phenotypes of A-Q complex mutants. Furthermore, unlike well-characterized A-Q complex proteins, SpoIIIL-GFP localizes uniformly in the forespore membrane before dispersing into the forespore cytoplasm. A synthetic sporulation screen identified a genetic relationship between spoIIIL and murAB, a paralog of murAA, required for efficient peptidoglycan precursor synthesis during sporulation. Cytological analysis indicates that the spoIIIL murAB double mutant is severely defective in the assembly of spore cortex peptidoglycan. Investigations into how SpoIIIL affects the cortex suggest it contributes to the activity of SpoIVB, a secreted forespore protease that initiates the signalling pathway required for processing of inactive pro-σK to active σK in the mother cell, which in turn up-regulates peptidoglycan precursor synthesis required for cortex formation. Accordingly, the spoIIIL mutant exhibits delayed and reduced pro-σK processing and decreased accumulation of peptidoglycan precursors. Thus, cortex assembly defects in the spoIIIL murAB double mutant results from alterations in separate pathways contributing to peptidoglycan precursor synthesis. Finally, phylogenetic analyses reveal that SpoIIIL is restricted to a subset of Bacillales species, highlighting evolutionary specialization in the signalling pathway leading to σK activation. Collectively, our findings redefine SpoIIIL as a forespore factor required for efficient cell-cell signalling that controls late mother-cell transcription.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011768"},"PeriodicalIF":4.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561672","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":"Ubp2 modulates DJ-1-mediated redox-dependent mitochondrial dynamics in Saccharomyces cerevisiae.","authors":"Sananda Biswas, Patrick D'Silva","doi":"10.1371/journal.pgen.1011353","DOIUrl":"10.1371/journal.pgen.1011353","url":null,"abstract":"<p><p>Mitochondrial integrity is a crucial determinant of overall cellular health. Mitochondrial dysfunction and impediments in regulating organellar homeostasis contribute majorly to the pathophysiological manifestation of several neurological disorders. Mutations in human DJ-1 (PARK7) have been implicated in the deregulation of mitochondrial homeostasis, a critical cellular etiology observed in Parkinson's disease progression. DJ-1 is a multifunctional protein belonging to the DJ-1/ThiJ/PfpI superfamily, conserved across the phylogeny. Although the pathophysiological significance of DJ-1 has been well-established, the underlying molecular mechanism(s) by which DJ-1 paralogs modulate mitochondrial maintenance and other cellular processes remains elusive. Using Saccharomyces cerevisiae as the model organism, we unravel the intricate mechanism by which yeast DJ-1 paralogs (collectively called Hsp31 paralogs) modulate mitochondrial homeostasis. Our study establishes a genetic synthetic interaction between Ubp2, a cysteine-dependent deubiquitinase, and DJ-1 paralogs. In the absence of DJ-1 paralogs, mitochondria adapt to a highly tubular network due to enhanced expression of Fzo1. Intriguingly, the loss of Ubp2 restores the mitochondrial integrity in the DJ-1 deletion background by modulating the ubiquitination status of Fzo1. Besides, the loss of Ubp2 in the absence of DJ-1 restores mitochondrial respiration and functionality by regulating the mitophagic flux. Further, Ubp2 deletion makes cells resistant to oxidative stress without DJ-1 paralogs. For the first time, our study deciphers functional crosstalk between Ubp2 and DJ-1 in regulating mitochondrial homeostasis and cellular health.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011353"},"PeriodicalIF":4.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561673","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":"Phenotypic tolerance for rDNA copy number variation within the natural range of C. elegans.","authors":"Ashley N Hall, Elizabeth A Morton, Rebecca Walters, Josh T Cuperus, Christine Queitsch","doi":"10.1371/journal.pgen.1011759","DOIUrl":"10.1371/journal.pgen.1011759","url":null,"abstract":"<p><p>The genes for ribosomal RNA (rRNA) are encoded by ribosomal DNA (rDNA), whose structure is notable for being present in arrays of tens to thousands of tandemly repeated copies in eukaryotic genomes. The exact number of rDNA copies per genome is highly variable within a species, with differences between individuals measuring in potentially hundreds of copies and megabases of DNA. The extent to which natural variation in rDNA copy number impacts whole-organism phenotypes such as fitness and lifespan is poorly understood, in part due to difficulties in manipulating such large and repetitive tracts of DNA even in model organisms. Here, we used the natural resource of copy number variation in C. elegans wild isolates to generate new tools and investigated the phenotypic consequences of this variation. Specifically, we generated a panel of recombinant inbred lines (RILs) using a laboratory strain derivative with ~130 haploid rDNA copies and a wild isolate with ~417 haploid rDNA copies, one of the highest validated C. elegans rDNA copy number arrays. We find that rDNA copy number is stable in the RILs, rejecting prior hypotheses that predicted copy number instability and copy number reversion. To isolate effects of rDNA copy number on phenotype, we produced a series of near isogenic lines (NILs) with rDNA copy numbers representing the high and low end of the rDNA copy number spectrum in C. elegans wild isolates. We find no correlation between rDNA copy number and phenotypes of rRNA abundance, competitive fitness, early life fertility, lifespan, or global transcriptome under standard laboratory conditions. These findings demonstrate a remarkable ability of C. elegans to tolerate substantial variation in a locus critical to fundamental cell function. Our study provides strain resources for future investigations into the boundaries of this tolerance.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011759"},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555405","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":"Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops.","authors":"José Antonio Mérida-Cerro, Guillaume Chevreux, Benoit Palancade, Ana G Rondón, Andrés Aguilera","doi":"10.1371/journal.pgen.1011491","DOIUrl":"10.1371/journal.pgen.1011491","url":null,"abstract":"<p><p>Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose expression levels are important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in CBP80-containing mRNPs formed in the absence of THO. In addition, we found that an excess of the RNA exosome component Dis3 impairs its function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011491"},"PeriodicalIF":4.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555404","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":"The length and strength of compartmental interactions are modulated by condensin II activity.","authors":"Randi Isenhart, Son C Nguyen, Leah Rosin, Weihuan Cao, Patrick Walsh, Haris Muzaffar, Christopher E Ellison, Eric F Joyce","doi":"10.1371/journal.pgen.1011724","DOIUrl":"10.1371/journal.pgen.1011724","url":null,"abstract":"<p><p>The spatial organization of the genome is crucial for its function and integrity. Although the ring-like SMC complex condensin II has a well-documented role in organizing mitotic chromosomes, its function in interphase chromatin structure has remained more enigmatic. Using a combination of Oligopaint fluorescence in situ hybridization (FISH) and Hi-C, we show that altering condensin II levels in diploid Drosophila cells significantly changes chromosome architecture at large length scales between chromatin compartments. Notably, condensin II overexpression disrupts the robust boundary between heterochromatin and euchromatin, leading to interactions that span entire chromosomes. These interactions occur independent from transcriptional changes, suggesting that the mechanisms driving compartment formation and their interactions might be distinct aspects of genome organization. Our results provide new insights into the dynamic nature of chromosome organization and underscore the importance of condensin II in maintaining genomic stability.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011724"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545751","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":"STRIPAK complex defects result in pseudosexual reproduction in Cryptococcus neoformans.","authors":"Patricia P Peterson, Sarah Croog, Yeseul Choi, Sheng Sun, Joseph Heitman","doi":"10.1371/journal.pgen.1011774","DOIUrl":"10.1371/journal.pgen.1011774","url":null,"abstract":"<p><p>STRIPAK is an evolutionarily conserved signaling complex that coordinates diverse cellular processes across fungi and animals. In the human fungal pathogen Cryptococcus neoformans, STRIPAK was recently shown to play critical roles in maintaining genome stability and controlling both sexual and asexual development. In Cryptococcus, sexual reproduction is closely linked to virulence, and our findings demonstrate that the STRIPAK complex plays key roles in both processes. Here, we further investigate the specific roles of the STRIPAK catalytic subunit Pph22 and its regulatory partner Far8 during sexual development. We show that while pph22Δ mutants are defective in α-a sexual reproduction, exhibiting impaired meiotic progression and a failure to produce viable spores, deletion of PPH22 results in exclusive pseudosexual reproduction, with progeny inheriting nuclear genomes solely from the wild-type parent. This nuclear selection appears to result from haploinsufficiency of PPH22, in which the mutant nucleus is excluded following cell-cell fusion. Overexpression of PPG1, a related phosphatase, rescued growth and developmental defects in pph22Δ mutants, and restored the preference for α-a sexual reproduction over pseudosexual reproduction during mating, suggesting functional redundancy within the STRIPAK signaling network. Furthermore, deletion of FAR8, another component of the STRIPAK complex, also led to a high rate of pseudosexual reproduction during α-a sexual mating, reinforcing the role of STRIPAK in modulating reproductive modes in C. neoformans, possibly through regulating nuclear inheritance and meiotic progression. Transcriptomic profiling of pph22Δ and far8Δ mutants revealed dysregulation of genes involved in nuclear organization, DNA replication and repair, RNA processing, cell cycle progression, and morphogenesis, suggesting that STRIPAK disruption broadly impairs cellular programs important for faithful sexual reproduction. Together, these findings highlight the distinct contributions of STRIPAK to sexual reproduction in C. neoformans and suggest that disruptions of this complex affect genome integrity and inheritance mechanisms, with broader implications for fungal adaptation and pathogenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011774"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530660","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":"Flipping the switch on some of the slowest mutating genomes: Direct measurements of plant mitochondrial and plastid mutation rates in msh1 mutants.","authors":"Amanda K Broz, Mychaela M Hodous, Yi Zou, Patricia C Vail, Zhiqiang Wu, Daniel B Sloan","doi":"10.1371/journal.pgen.1011764","DOIUrl":"10.1371/journal.pgen.1011764","url":null,"abstract":"<p><p>Plant mitochondrial and plastid genomes have exceptionally slow rates of sequence evolution, and recent work has identified an unusual member of the MutS gene family (\"plant MSH1\") as being instrumental in preventing point mutations in these genomes. However, the effects of disrupting MSH1-mediated DNA repair on \"germline\" mutation rates have not been quantified. Here, we used Arabidopsis thaliana mutation accumulation (MA) lines to measure mutation rates in msh1 mutants and matched wild type (WT) controls. We detected 124 single nucleotide variants (SNVs: 49 mitochondrial and 75 plastid) and 668 small insertions and deletions (indels: 258 mitochondrial and 410 plastid) in msh1 MA lines at a heteroplasmic frequency of ≥ 20%. In striking contrast, we did not find any organelle mutations in the WT MA lines above this threshold, and reanalysis of data from a much larger WT MA experiment also failed to detect any variants. The observed number of SNVs in the msh1 MA lines corresponds to estimated mutation rates of 6.1 × 10-7 and 3.2 × 10-6 per bp per generation in mitochondrial and plastid genomes, respectively. These rates exceed those of species known to have very high mitochondrial mutation rates (e.g., nematodes and fruit flies) by an order of magnitude or more and are on par with estimated rates in humans despite the generation times of A. thaliana being nearly 100-fold shorter. Therefore, disruption of a single plant-specific genetic factor in A. thaliana is sufficient to erase or even reverse the enormous difference in organelle mutation rates between plants and animals.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011764"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530659","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":"Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis.","authors":"Saeko Takada, Bonnie J Bolkan, MaryJane O'Connor, Michael Goldberg, Michael B O'Connor","doi":"10.1371/journal.pgen.1011469","DOIUrl":"10.1371/journal.pgen.1011469","url":null,"abstract":"<p><p>Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined the function of Trus during Drosophila development. CRISPR/Cas9 generated null mutations in trus lead to partial embryonic lethality, significant larval developmental delay, and complete pre-pupal lethality. In mutant larvae, we found decreased cell proliferation and growth defects in the brain and imaginal discs. Mapping relevant tissues for Trus function using trus RNAi and trus mutant rescue experiments revealed that imaginal disc defects are primarily responsible for the developmental delay, while the pre-pupal lethality is likely associated with faulty central nervous system (CNS) development. Examination of the molecular mechanism behind the developmental delay phenotype revealed that trus mutations induce the Xrp1-Dilp8 ribosomal stress-response in growth-impaired imaginal discs, and this signaling pathway attenuates production of the hormone ecdysone in the prothoracic gland. Additional Tap-tagging and mass spectrometry of components in Trus complexes isolated from Drosophila Kc cells identified Ribosomal protein subunit 2 (RpS2), which is coded by string of pearls (sop) in Drosophila, and Eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) as interacting factors. We discuss the implication of these findings with respect to the similarity and differences in trus genetic null mutant phenotypes compared to the haplo-insufficiency phenotypes produced by heterozygosity for mutants in Minute genes and other genes involved in ribosome biogenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 6","pages":"e1011469"},"PeriodicalIF":4.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512638","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}