Zoological Research最新文献

Ring finger protein 122 (RNF122), an E3 ubiquitin ligase, orchestrates antiviral immune responses in mammals by targeting retinoic acid-inducible gene 1 and melanoma differentiation-associated gene 5 for ubiquitination. However, its functional relevance in teleosts has yet to be clearly defined, particularly regarding the identification of substrate-specific regulatory sites. This study characterized RNF122 from mandarin fish ( Siniperca chuatsi), termed scRNF122, and investigated its regulatory impact on stimulator of interferon genes (STING)-mediated antiviral signaling. Results showed that scRNF122 expression was up-regulated in response to mandarin fish ranavirus (MRV) infection, and its overexpression suppressed scSTING-mediated interferon (IFN) production and enhanced MRV replication. Co-immunoprecipitation confirmed a direct interaction between scRNF122 and scSTING. Functional assays demonstrated that scRNF122 facilitated scSTING degradation through the ubiquitin-proteasome pathway, a process impeded by MG132 treatment. Ubiquitination analyses of various scSTING mutants revealed that scRNF122 catalyzed scSTING ubiquitination at K95, K117, and K155 residues. Moreover, scRNF122 significantly impaired scSTING-dependent antiviral responses by engaging negative regulatory elements within the signaling cascade. Overall, scRNF122 was identified as a negative modulator of STING-mediated IFN signaling in mandarin fish, diminishing STING-dependent antiviral activity and promoting its degradation via the ubiquitin-proteasome pathway at lysine residues K95, K117, and K155. These findings provide mechanistic insight into the post-translational control of STING in teleosts and establish a foundation for future investigations into antiviral immune regulation.

Comprehensive phylogeographic insights require the integration of evidence across diverse taxa, ecosystems, and geographical regions. However, our understanding of the arid biota of the vast Asian drylands remains limited. Accordingly, this study combined phylogeographic analyses with ecological niche modeling to investigate patterns of diversification and demography of the Central Asian racerunner ( Eremias vermiculata), a widespread lizard inhabiting arid eastern-Central Asia (AECA). Mitochondrial DNA (mtDNA) sequences were obtained from 876 individuals across 113 localities, while three nuclear genes- CGNL1, MAP1A, and β-fibint7-were sequenced from 204, 170, and 138 individuals, respectively. Analyses identified four distinct mtDNA lineages corresponding to specific geographic subregions within the AECA, reflecting the topographic and ecological heterogeneity of the region. The detection of mito-nuclear discordance indicated the presence of complex evolutionary dynamics. Divergence dating placed the initial lineage splits at approximately 1.18 million years ago, coinciding with major tectonic activity and climatic aridification that likely promoted allopatric divergence. In particular, lineage diversification within the Tarim Basin suggests that recent environmental shifts may have contributed to genetic divergence. Demographic reconstructions revealed signatures of population expansion or range shifts across all lineages during the Last Glacial Maximum, signifying the combined influence of the unique topography and climate dynamics of the AECA on diversification and demographic change. These results highlight the need for fine-scale genomic investigations to clarify the mechanisms underlying mito-nuclear discordance and local adaptation. Such efforts are essential for advancing understanding of how genetic diversity in dryland taxa responds to environmental change, providing insights into the evolutionary adaptability of species in dynamic landscapes.

Chorionic gonadotropin α (Cgα) functions as the shared subunit for thyroid-stimulating hormone subunit β (Tshβ), luteinizing hormone subunit β (Lhβ), and follicle-stimulating hormone subunit β (Fshβ). While these β-subunits have been extensively studied using effective gene knockout models in zebrafish, the biological role of Cgα remains elusive. In this study, cgα-deficient zebrafish generated via transcription activator-like effector nucleases (TALENs) exhibited viability but displayed pronounced developmental abnormalities, including growth retardation, hyperpigmentation, reduced thyroxine (T4) levels, and defective anterior swim bladder inflation during juvenile stages. In adults, cgα deficiency led to disrupted gonadal development, impaired secondary sex characteristics (SSCs), and severely impacted reproductive behavior in both female and male fish. Notably, both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ ^-/- ; fshβ ^-/- mutants. Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ ( cgα ^-/-; fshβ ^-/-), marked by elevated anti-Müllerian hormone ( amh) expression, or following loss of follicle-stimulating hormone receptor ( fshr) ( cgα ^-/-; fshr ^-/-). In vitro assays in Chinese hamster ovary (CHO) cells revealed increased cAMP response element (CRE) promoter activity following transfection with constructs encoding Fshr, Fshβ/Fshr, or Cgα/Fshβ/Fshr. Collectively, the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin- and gonadotropin-disrupted models, highlighting the essential role of Cgα in thyroid and gonadal function. Importantly, these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish, including Cgα-independent Fshβ activity and the constitutive functionality of Fshr.

The DNA replication stress (RS) response is crucial for maintaining cellular homeostasis and promoting physiological longevity. However, the mechanisms by which long-lived species, such as bats, regulate RS to maintain genomic stability remain unclear. Also, recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability. In this study, somatic skin fibroblasts from the long-lived big-footed bat ( Myotis pilosus) were examined, with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells. Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences, including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway. These features emphasize a distinct homeostatic strategy in bat cells. Nuclear fragile X mental retardation-interacting protein 1 ( Nufip1), a ribosome-associated factor highly expressed in bat fibroblasts, was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like (Rps27l). These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats, highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.

Bromodomain (BRD)-containing proteins are central mediators of gene regulation, serving as key components of chromatin remodeling complexes and histone recognition scaffolds. By specifically recognizing acetylated lysine residues on histones (Kac) via their conserved BRD, these proteins influence chromatin structure and gene expression. Although their overarching role is well-established, the precise molecular functions and mechanisms of individual BRD proteins remain incompletely characterized. The ciliate Tetrahymena thermophila, a unicellular eukaryote with a transcriptionally active macronucleus enriched in histone acetylation, is an excellent model for exploring the significance of BRD-containing proteins. In this comprehensive review, all BRD-containing proteins encoded in the T. thermophila genome are systematically examined, including their expression profiles, histone acetylation targets, interacting proteins, and potential roles. This review lays the groundwork for future investigations into the complex roles of BRD proteins in chromatin remodeling and transcription regulation, offering insights into basic eukaryotic biology and the molecular mechanisms underlying BRD-linked diseases.

The yellow boxfish ( Ostracion cubicus) exhibits a combination of derived morphological traits specialized for coral reef environments and ancestral characteristics, including a fused dermal plate. Contradictory evolutionary evidence hinders true classification of O. cubicus. To clarify its evolutionary position within Tetraodontiformes, a chromosome-level genome assembly was generated, representing the most contiguous and complete genome to date for this lineage. Notably, O. cubicus possessed the largest genome within the order Tetraodontiformes, primarily due to extensive transposable element expansion. Phylogenetic analysis based on 19 whole genomes and 131 mitochondrial genomes resolved Tetraodontiformes into three major sister groups (Ostraciidae-Molidae, Tetraodontidae, and Balistidae-Monacanthidae). Comparative genomic evidence indicated that O. cubicus diverged early from the common ancestor of modern Tetraodontiformes and retained the highest number of HOX genes among surveyed taxa. Although overall genomic architecture was largely conserved, certain genetic and environmental changes may have contributed to its phenotypic adaptations, including climate cooling during the Miocene-Pliocene Transition, recent DNA and long interspersed nuclear element (LINE) transposon bursts, lineage-specific chromosomal rearrangements, and gene family expansion. Many positively selected genes and rapidly evolving genes were associated with skeletal development, including bmp7, egf7, and bmpr2. Transcriptomic comparisons between carapace and tail skin revealed various candidate genes and pathways related to carapace formation, such as postn, scpp1, and components of the TGF-β signaling pathway. A derived amino acid substitution in eda, coupled with protein structural modeling, suggested potential molecular convergence in dermal plate formation among teleosts. These findings provide novel insights into the genomic and developmental basis of carapace evolution and coral reef-adaptation in O. cubicus, offering a strong case for evolutionary balance between genomic conservation with regulatory innovation to achieve coral reef specialization.

NORHA, a long non-coding RNA (lncRNA), serves as a key inducer of follicular atresia in sows by triggering granulosa cells (GCs) apoptosis. However, its regulation by N6-methyladenosine (m6A)-the most abundant RNA modification-remains unresolved. This study identified NORHA as a functional target of the m6A reader HNRNPA2B1 in sow GCs (sGCs). Transcriptome-wide mapping of RNA modification sites revealed extensive m6A enrichment on NORHA, with HNRNPA2B1 binding directly to the transcript and enhancing its stability via modification of multiple m6A sites, including A261, A441, and A919. HNRNPA2B1 suppressed 17β-estradiol (E2) biosynthesis and promoted sGC apoptosis by activating the NORHA-FoxO1 axis. FoxO1 subsequently repressed expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), which encodes the enzyme essential for E2 biosynthesis. Additionally, HNRNPA2B1 functioned as a critical mediator of METTL3-dependent m6A modification, modulating NORHA expression and activity in sGCs. This study highlights an important m6A-dependent regulatory mechanism governing NORHA expression in sGCs.

Vertebrate limbs have undergone profound morphological diversification, enabling adaptations to a broad spectrum of ecological niches. In marine mammals, the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats. This adaptation has been hypothesized to result, in part, from the inhibition of interphalangeal cell apoptosis during limb development, although the underlying genetic mechanism remains poorly understood. This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes, BMP2, BMP4, and BMP7, which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues. Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage, with two positively selected sites (V79I and H247R) involved in cetacean-specific amino acid substitutions located in the TGF-β propeptide functional domain in BMP4. In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors, including cytochrome c (Cyt c), BCL2 associated X, and B-cell lymphoma 2, within the BMP signaling pathway. The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.

Photodynamic therapy (PDT) is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen, leading to the generation of reactive oxygen species (ROS). This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts. However, the broader clinical applications remain limited by photosensitizer selectivity, shallow light penetration, and the risk of off-target cytotoxicity. Recent advancements in PDT have focused on the development of next-generation photosensitizers, the integration of nanotechnology for enhanced delivery and targeting, and the strategic combination of PDT with complementary therapeutic approaches. Experimental animal models play a crucial role in validating the efficacy and safety of PDT, optimizing its therapeutic parameters, and determining its mechanisms of action. This review provides a comprehensive overview of PDT applications in various disease models, including oncological, infectious, and nonconventional indications. Special emphasis is placed on the importance of large animal models in PDT research, such as rabbits, pigs, dogs, and non-human primates, which provide experimental platforms that more closely resemble human physiological and pathological states. The use of these models for understanding the mechanisms of PDT, optimizing therapeutic regimens, and evaluating clinical outcomes is also discussed. This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.

Ectothermic organisms may expand their thermal tolerance by producing multiple protein isoforms with differing thermal sensitivities. While such isoforms commonly originate from allelic variation at a single locus (allozymes) or from gene duplication that gives rise to paralogs with distinct thermal responses, this study investigated mRNA editing as an alternative, post-transcriptional mechanism for generating mRNA variants. Cytosolic malate dehydrogenase (cMDH) was examined in foot tissue of two congeners of the marine mussel genus Mytilus, which occupy different thermal environments. Multiple editing events were detected within the mRNA coding region in both species. Editing sites were species-specific, with no shared positions identified. In M. coruscus, editing occurred at 117, 123, 135, 190, 195, 204, 279, and 444, while in M. galloprovincialis, editing was detected at 216 and 597. Each species exhibited multiple edited mRNA variants, and these isoforms were associated with differential protein expression. These findings suggest that mRNA editing may contribute an additional layer of molecular variation. The generation of diverse mRNA isoforms from a single DNA coding sequence may enhance enzymatic flexibility across temperature ranges, supporting eurythermal physiological performance and mitigating thermal stress. Moreover, the presence of multiple edited transcripts within individual organisms raises important caveats about the limitations of approaches that deduce amino acid sequences or estimate adaptive variation solely from genomic data.