Search Results (24)

SERBP1 (SERPINE1 mRNA-Binding Protein 1), as an RNA-binding protein with multiple biological functions, has become a research hotspot in the field of life sciences in recent years. Its unique molecular structure, such as the presence of RG/RGG repeat sequences and the absence of typical RNA-binding domains, enables it to exert diverse roles in cells. This article systematically reviews the research progress of SERBP1 in various fields including cellular stress response, tumorigenesis and development, reproductive system regulation, nervous system function, and viral infection, elaborates on its mechanism of action in detail (including newly supplemented content on cell cycle regulation, interaction with PARP1, and ribosome biogenesis), and outlines future research directions. It aims to provide a reference for in-depth understanding of the biological functions of SERBP1 and the diagnosis and treatment of related diseases. Full article

Pharmacological chaperones of heterogeneous nuclear ribonucleoproteins (hnRNPs) show promise as potential neuroprotective drug candidates. They are expected to prevent the accumulation of neurotoxic hnRNP biocondensates and aggregates, which are hallmarks of severe degenerative diseases. Here, we present the first rational design of oligonucleotide chaperones of hnRNP A1. This design was inspired by previous studies on the specificity of the RNA recognition motif (RRM) and the RGG motif of hnRNP A1 for endogenous nucleic acids. To obtain robust and specific chaperones, we combined an RRM-binding sequence with an RGG-binding G-quadruplex oligonucleotide that inhibits hnRNP A1 aggregation and introduced various modifications into the sugar-phosphate backbone of the oligonucleotide. Modifications that locked the RRM-binding sequence in a conformational state characteristic of RNA improved chaperone affinity and activity. The former was assessed using microscale thermophoresis assays, while the latter was evaluated using fluorimetry and microscopy. The leading chaperone bound to hnRNP A1 at micromolar concentrations and inhibited the assembly of its condensates and amyloid-like aggregates (fibrils) by over 90%. Full article

Acetate may act as a signaling molecule, regulating Paracin 1.7 production via quorum sensing (QS) in Lacticaseibacillus paracasei HD1.7. The “acetate switch” phenomenon requires mechanistic exploration to optimize Paracin 1.7 production. The “acetate switch” phenomenon delays with higher glucose levels (30 h, 36 h, and 96 h). Before the occurrence of the “acetate switch”, the ATP content increases and peaks at the “acetate switch” point and the NAD⁺/NADH ratio decreases, indicating energy changes. Moreover, the QS genes used for the pre-regulation of bacteriocin, such as prcKR, comCDE, were highly expressed. After the “acetate switch”, the ATP content decreased and the QS genes for the post-regulation of bacteriocin were highly expressed, such as rggs234 and sigma70-1/70-2. The “acetate switch” could act as an energy switch, regulating bacterial growth and QS genes. Before and after the “acetate switch”, some metabolic pathways were significantly altered according to the transcriptomic analysis by HD1.7 and HD1.7-Δpta. In this study, acetate was used as an input signal to regulate the two-component system, significantly influencing the bacteriocin expression system. And this study clarifies the roles of acetate, energy, and quorum sensing in promoting Paracin 1.7 production, providing a theoretical basis for optimizing the bacteriocin fermentation process of HD1.7. Full article

Monocular depth estimation (MDE) has emerged as a powerful technique for extracting scene depth from a single image, particularly in the context of computational imaging. Conventional MDE methods based on RGB images often degrade under varying illuminations. To overcome this, an end-to-end framework is developed that leverages the illumination-invariant properties of infrared images for accurate depth estimation. Specifically, a multi-task UNet architecture was designed to perform gradient extraction, semantic segmentation, and texture reconstruction from infrared RAW images. To strengthen structural learning, a Radiation Field Gradient Guidance (RGG) module was incorporated, enabling edge-aware attention mechanisms. The gradients, semantics, and textures were mapped to the Saturation (S), Hue (H), and Value (V) channels in the HSV color space, subsequently converted into an RGB format for input into the depth estimation network. Additionally, a sky mask loss was introduced during training to mitigate the influence of ambiguous sky regions. Experimental validation on a custom infrared dataset demonstrated high accuracy, achieving a ${\delta }_1$ of 0.976. These results confirm that integrating radiation field gradient guidance and semantic priors in HSV space significantly enhances depth estimation performance for infrared imagery. Full article

R2 retrotransposons reside exclusively within the 28S regions of 10–20% of all rDNA genes comprising the nucleolar organizer loci on the X and Y chromosomes of Drosophila melanogaster. These R2-inserted genes are normally silent and heterochromatic. When expressed, however, the R2 transcript is co-transcribed with the 28S rRNA. Self-cleavage releases a 3.6 kb mature R2 transcript that encodes a single protein with endonuclease and reverse transcriptase activities that facilitate R2 element transposition by target-primed reverse transcription. While we know the molecular details of R2 transposition, we know little about the genetic mechanisms that initiate R2 transcription. Here, we examine R2 expression in wild type versus mutant backgrounds. R2 expression in stage 1–4 wild type egg chambers was variable depending on the stock. R2 expression was silent in wild type stages 5–10 but was consistently active during nurse cell nuclear breakdown in stages 12–13 regardless of the genetic background. Massive R2 expression occurred in stages 5–10 upon loss of Udd, an RNA Pol I transcription factor. Similarly, loss of Nopp140, an early ribosome assembly factor, induced R2 expression more so in somatic tissues. Interestingly, over-expression of the Nopp140-RGG isoform but not the Nopp140-True isoform induced R2 expression in larval somatic tissues, suggesting Nopp140-RGG could potentially affect rDNA chromatin structure. Conversely, Minute mutations in genes encoding ribosomal proteins had minor positive effects on R2 expression. We conclude that R2 expression is largely controlled by factors regulating RNA Pol I transcription and early ribosome assembly. Full article

Porcine circovirus type 2 (PCV2) is a significant pathogen responsible for porcine circovirus-associated diseases (PCVAD), and it is widely prevalent in pig farms, leading to huge economic losses for the pig industry. Currently, the ability of PCV2 to enhance its own replication by using the antiviral inflammatory factors IFNα, IFNβ, and IL-2 and its complex immune escape mechanism remain unclear, which has attracted wide attention. Research has indicated that GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is involved in the innate immune response to a variety of viruses, primarily by regulating and composing stress granules (SGs) to inhibit viral replication. Our initial studies identified elevated G3BP1 expression during PCV2 infection, paradoxically promoting PCV2 replication. In light of this phenomenon, this study aims to elucidate how PCV2 regulates G3BP1 to enhance its replication. Our findings demonstrate that G3BP1 overexpression further activates PCV2-induced expression of RIG-I, MDA5, cGAS and STING, thereby promoting IFNβ production and affecting cell cycle arrest in the S phase, facilitating PCV2 replication. Moreover, interactions were observed between PCV2 Cap protein and G3BP1’s RGG domain, and between PCV2 Rep protein and G3BP1’s NTF2 and RRM domains, potentially promoting viral protein nuclear transfer. In summary, PCV2 enhances its replication by modulating G3BP1 to induce IFNβ production and directly binds viral proteins to promote viral protein nuclear transfer. This research provides a foundation for further investigation into the immune evasion mechanisms of PCV2. Full article

Just and fair transitions to low-carbon and nature-positive ways of living need to occur fast enough to limit and reverse the climate and nature crises, but not so fast that the public is left behind. We propose the concept of “Regenerative Good Growth” (RGG) to replace the language and practice of extractive, bad GDP growth. RGG centres on the services provided by five renewable capitals: natural, social, human, cultural, and sustainable physical. The term “growth” tends to divide rather than unite, and so here we seek language and storylines that appeal to a newly emergent climate-concerned majority. Creative forms of public engagement that lead to response diversity will be essential to fostering action: when people feel coerced into adopting single options at pace, there is a danger of backlash or climate authoritarianism. Policy centred around storytelling can help create diverse public responses and institutional frameworks. The practises underpinning RGG have already created business opportunities, while delivering sharp falls in unit costs. Fast transitions and social tipping points are emerging in the agricultural, energy, and city sectors. Though further risks will emerge related to rebound effects and lack of decoupling of material consumption from GDP, RGG will help cut the externalities of economies. Full article

Background: Femoral torsional malalignment is a common cause of in-toeing and out-toeing in children, often leading to gait disturbances, functional limitations, and increased risk of falls. Traditionally, osteotomy was the only surgical option for correction. A minimally invasive technique known as rotational guided growth (RGG) has recently been introduced to address these malalignments. This study aims to assess the effectiveness of rotational femoral malalignment correction by rotational epiphysiodesis with tension band 8-plates (Orthofix, Verona, Italy). Methods: Eleven patients with in-toeing and out-toeing (19 femurs) were treated using RGG with 8-plates. The 8-plates were applied laterally and medially, with screws placed above and below the growth plate of the distal femur, angled obliquely to the long axis of the bone in opposite directions. Changes in foot progression angle (FPA), femoral version, the alteration in the angle between the 8-plates, and the rate of correction were recorded. Results: All patients reported functional gait improvement. The FPA was corrected from a mean of 32 degrees to 7 degrees, the femoral version improved from a mean of 60 degrees to 22 degrees. The angle between the 8-plates changed from a mean of 75 degrees to 28 degrees, with a correction rate of 4.1 degrees per month. The average time for correction was 11 months. No complications were observed during the treatment. Conclusions: RGG using 8-plates is a novel, minimally invasive surgical technique that effectively corrects rotational femoral deformities and may serve as a preferred alternative to derotational osteotomy in growing patients. Full article

Abnormal intracellular phase transitions in mutant hnRNP A1 may underlie the development of several neurodegenerative diseases. The risk of these diseases increases upon C9Orf72 repeat expansion and the accumulation of the corresponding G-quadruplex (G4)-forming RNA, but the link between this RNA and the disruption of hnRNP A1 homeostasis has not been fully explored so far. Our aim was to clarify the mutual effects of hnRNP A1 and C9Orf72 G4 in vitro. Using various optical methods and atomic force microscopy, we investigated the influence of the G4 on the formation of cross-beta fibrils by the mutant prion-like domain (PLD) of hnRNP A1 and on the co-separation of the non-mutant protein with a typical SR-rich fragment of a splicing factor (SRSF), which normally drives the assembly of nuclear speckles. The G4 was shown to act in a holdase-like manner, i.e., to restrict the fibrillation of the hnRNP A1 PLD, presumably through interactions with the PLD-flanking RGG motif. These interactions resulted in partial unwinding of the G4, suggesting a helicase-like activity of hnRNP A1 RGG. At the same time, the G4 was shown to disrupt hnRNP A1 co-separation with SRSF, suggesting its possible contribution to pathology through interference with splicing regulation. Full article

Glycine- and arginine-rich (GAR) motifs with different combinations of RG/RGG repeats are present in many proteins. The nucleolar rRNA 2′-O-methyltransferase fibrillarin (FBL) contains a conserved long N-terminal GAR domain with more than 10 RGG plus RG repeats separated by specific amino acids, mostly phenylanalines. We developed a GAR motif finder (GMF) program based on the features of the GAR domain of FBL. The G(0,3)-X(0,1)-R-G(1,2)-X(0,5)-G(0,2)-X(0,1)-R-G(1,2) pattern allows the accommodation of extra-long GAR motifs with continuous RG/RGG interrupted by polyglycine or other amino acids. The program has a graphic interface and can easily output the results as .csv and .txt files. We used GMF to show the characteristics of the long GAR domains in FBL and two other nucleolar proteins, nucleolin and GAR1. GMF analyses can illustrate the similarities and also differences between the long GAR domains in the three nucleolar proteins and motifs in other typical RG/RGG-repeat-containing proteins, specifically the FET family members FUS, EWS, and TAF15 in position, motif length, RG/RGG number, and amino acid composition. We also used GMF to analyze the human proteome and focused on the ones with at least 10 RGG plus RG repeats. We showed the classification of the long GAR motifs and their putative correlation with protein/RNA interactions and liquid–liquid phase separation. The GMF algorithm can facilitate further systematic analyses of the GAR motifs in proteins and proteomes. Full article

Although SRPKs were discovered nearly 30 years ago, our understanding of their mode of regulation is still limited. Regarded as constitutively active enzymes known to participate in diverse biological processes, their prominent mode of regulation mainly depends on their intracellular localization. Molecular chaperones associate with a large internal spacer sequence that separates the bipartite kinase catalytic core and modulates the kinases’ partitioning between the cytoplasm and nucleus. Besides molecular chaperones that function as anchoring proteins, a few other proteins were shown to interact directly with SRPK1, the most-studied member of SRPKs, and alter its activity. In this study, we identified TAF15, which has been involved in transcription initiation, splicing, DNA repair, and RNA maturation, as a novel SRPK1-interacting protein. The C-terminal RGG domain of TAF15 was able to associate with SRPK1 and downregulate its activity. Furthermore, overexpression of this domain partially relocalized SRPK1 to the nucleus and resulted in hypophosphorylation of SR proteins, inhibition of splicing of a reporter minigene, and inhibition of Lamin B receptor phosphorylation. We further demonstrated that peptides comprising the RGG repeats of nucleolin, HNRPU, and HNRNPA2B1, were also able to inhibit SRPK1 activity, suggesting that negative regulation of SRPK1 activity might be a key biochemical property of RGG motif-containing proteins. Full article

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer. Full article

Bacteriocins from lactic acid bacteria are natural preservatives that inhibit foodborne pathogenic microorganisms. Co-culture is a form of population competition to induce bacteriocin production. In this study, we aimed to investigate the regulatory response of Lactaseibacillus paracasei HD1.7 to population competition and examine acetic stress during bacteriocin production. The cell-free supernatant of Bacillus subtilis positively and negatively regulated L. paracasei HD1.7 bacteriocin production, which depended on the growth period of B. subtilis ATCC 11774 and the addition ratio of the cell-free supernatant. We found that L. paracasei HD1.7 sensed B. subtilis ATCC 11774 through the cell-free supernatant, and then, acetic acid was secreted to promote bacteriocin production. There was a close connection between acetic acid metabolism and the bacteriocin regulatory system. In addition, transcriptomic analysis revealed that the functions of the transcriptional regulators rgg and rpoD in the bacteriocin regulatory system were enhanced with increasing acetic acid stress concentration. Collectively, the results of this study increase our current understanding of L. paracasei HD1.7 bacteriocin production and provide insights into high bacteriocin production by co-culture or acetic acid induction. Full article

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that threats the majority of the world’s population. Poly (ADP-ribose) polymerase 1 (PARP-1) and protein poly (ADP-ribosyl)ation (PARylation) regulates manifold cellular functions. The role of PARP-1 and protein PARylation in HCMV infection is still unknown. In the present study, we found that the pharmacological and genetic inhibition of PARP-1 attenuated HCMV replication, and PARG inhibition favors HCMV replication. PARP-1 and its enzymatic activity were required for efficient HCMV replication. HCMV infection triggered the activation of PARP-1 and induced the translocation of PARP-1 from nucleus to cytoplasm. PARG was upregulated in HCMV-infected cells and this upregulation was independent of viral DNA replication. Moreover, we found that HCMV UL76, a true late protein of HCMV, inhibited the overactivation of PARP-1 through direct binding to the BRCT domain of PARP-1. In addition, UL76 also physically interacted with poly (ADP-ribose) (PAR) polymers through the RG/RGG motifs of UL76 which mediates its recruitment to DNA damage sites. Finally, PARP-1 inhibition or depletion potentiated HCMV-triggered induction of type I interferons. Our results uncovered the critical role of PARP-1 and PARP-1-mediated protein PARylation in HCMV replication. Full article

The vasa gene is essential for germ cell development and gametogenesis both in vertebrates and in invertebrates. In the present study, vasa (Rcvasa) cDNA was cloned from cobia (Rachycentron canadum) using the RACE amplification method. We found that the full-length cDNA sequence of Rcvasa comprises 2571 bp, containing a 5′-UTR of 145 bp, a 3′-UTR of 341 bp, and an open reading frame (ORF) of 2085 bp, encoding a protein of 694 aa. The deduced amino acid sequence contains 8 conserved motifs of the DEAD-box protein family, 7 RGG repeats, and 10 RG repeats in the N-terminal region. Comparisons of the deduced amino acid sequence with those of other teleosts revealed the highest percentage identity (86.0%) with Seriola quinqueradiata. By using semiquantitative RT-PCR, Rcvasa appeared to be specifically expressed in the testis and ovary, among 13 tissues analyzed. In addition, annual changes in Rcvasa expression levels were examined in the gonads by quantitative real-time PCR (qRT-PCR). The expression of Rcvasa in the testis first increased significantly at 120 dph (stage II–III), then stabilized as the testis developed from 185 dph (stage III) to 360 dph (stage V). During the development of the ovary (stage I to II), the expression of Rcvasa first increased and reached the highest level at 210 dph (stage II), then decreased. Furthermore, the results of chromogenic in situ hybridization (CISH) revealed that Rcvasa mRNA was mainly expressed in germ cells and barely detected in somatic cells. In the testis, Rcvasa mRNA signal was concentrated in the periphery of spermatogonia, primary spermatocytes, and secondary spermatocytes and was significantly weaker in spermatids and spermatozoa. In the ovary, Rcvasa mRNA signal was uniformly distributed in the perinuclear cytoplasm and was intense in early primary oocytes (stage I and II). These findings could provide a reference for understanding the regulatory mechanisms of vasa expression during the development of germ cells in cobia. Full article