Ribosomal Protein L11 Research Articles

RiboScreenTM Technology Delivers a Ribosomal Target and a Small-Molecule Ligand for Ribosome Editing to Boost the Production Levels of Tropoelastin, the Monomeric Unit of Elastin.

Elastin, a key structural protein essential for the elasticity of the skin and elastogenic tissues, degrades with age. Replenishing elastin holds promise for anti-aging cosmetics and the supplementation of elastic activities of the cardiovascular system. We employed RiboScreenTM, a technology for identifying molecules that enhance the production of specific proteins, to target the production of tropoelastin. We make use of RiboScreenTM in two crucial steps: first, to pinpoint a target ribosomal protein (TRP), which acts as a switch to increase the production of the protein of interest (POI), and second, to identify small molecules that activate this ribosomal protein switch. Using RiboScreenTM, we identified ribosomal protein L40, henceforth eL40, as a TRP switch to boost tropoelastin production. Drug discovery identified a small-molecule hit that binds to eL40. In-cell treatment demonstrated activity of the eL40 ligand and delivered increased tropoelastin production levels in a dose-dependent manner. Thus, we demonstrate that RiboScreenTM can successfully identify a small-molecule hit capable of selectively enhancing tropoelastin production. This compound has the potential to be developed for topical or systemic applications to promote skin rejuvenation and to supplement elastic functionality within the cardiovascular system.

Ribosomal protein L17 functions as an antimicrobial protein in amphioxus

Antimicrobial peptides (AMPs), characterized by their cationic nature and amphiphilic properties, play a pivotal role in inhibiting the biological activity of microbes. Currently, only a fraction of the antimicrobial potential within the ribosomal protein family has been explored, despite its extensive membership and resemblance to AMPs. Herein we demonstrated that amphioxus RPL17 (BjRPL17) exhibited not only upregulated expression upon bacterial stimulation but also possessed bactericidal capabilities against both Gram-negative and -positive bacteria through combined action mechanisms including interaction with cell surface molecules LPS, LTA, and PGN, disruption of cell membrane integrity, promotion of membrane depolarization, and induction of intracellular ROS production. Furthermore, a peptide derived from residues 127–141 of BjRPL17 (termed BjRPL17-1) showed antibacterial activity against Staphylococcus aureus and its methicillin-resistant strain via the same mechanism observed for the full-length protein. Additionally, the rpl17 gene was highly conserved in Metazoa, hinting it may play a universal role in the antibacterial defense system in different animals. Importantly, neither BjRPL17 nor peptide BjRPL17-1 exhibited toxicity towards mammalian cells thereby offering prospects for designing novel AMP agents based on these findings. Collectively, our results establish RPL17 as a novel member of AMPs with remarkable evolutionary conservation.

SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.

Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. 3) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in samples from patients with GAC and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease, including peritoneal carcinomatosis. Suppressing SMYD5 methylation of rpL40 inhibits human cancer cell and patient-derived GAC xenograft growth and renders them hypersensitive to inhibitors of PI3K and mTOR. Finally, combining SMYD5 depletion with PI3K-mTOR inhibition and chimeric antigen receptor T cell administration cures an otherwise lethal in vivo mouse model of aggressive GAC-derived peritoneal carcinomatosis. Together, our work uncovers a ribosome-based epigenetic mechanism that facilitates the evolution of malignant GAC and proposes SMYD5 targeting as part of a potential combination therapy to treat this cancer.

Involvement of ribosomal protein L17 and Y-box binding protein 1 in the assembly of hepatitis C virus potentially via their interaction with the 3' untranslated region of the viral genome.

Although basic research on the HCV life cycle has progressed significantly over the past two decades, our understanding of the molecular mechanisms that regulate the process of particle formation, in particular encapsidation of the genome or nucleocapsid assembly, has been limited. We present here, for the first time, that two RNA-binding proteins, RPL17 and YBX1, bind to the 3'X in the 3'UTR of the HCV genome, which potentially acts as a packaging signal, and facilitates the viral particle assembly. Our study revealed that RPL17 and YBX1 exert a positive effect on the interaction between HCV RNA and Core protein, suggesting that the presence of both host factors modulate an RNA structure or conformation suitable for packaging the viral genome. These findings help us to elucidate not only the regulatory mechanism of the particle assembly of HCV but also the function of host RNA-binding proteins during viral infection.

Genome-Wide Association Studies on Resistance to Pea Weevil: Identification of Novel Sources of Resistance and Associated Markers.

Little resistance to the pea weevil insect pest (Bruchus pisorum) is available in pea (Pisum sativum) cultivars, highlighting the need to search for sources of resistance in Pisum germplasm and to decipher the genetic basis of resistance. To address this need, we screened the response to pea weevil in a Pisum germplasm collection (324 accession, previously genotyped) under field conditions over four environments. Significant variation for weevil seed infestation (SI) was identified, with resistance being frequent in P. fulvum, followed by P. sativum ssp. elatius, P. abyssinicum, and P. sativum ssp. humile. SI tended to be higher in accessions with lighter seed color. SI was also affected by environmental factors, being favored by high humidity during flowering and hampered by warm winter temperatures and high evapotranspiration during and after flowering. Merging the phenotypic and genotypic data allowed genome-wide association studies (GWAS) yielding 73 markers significantly associated with SI. Through the GWAS models, 23 candidate genes were found associated with weevil resistance, highlighting the interest of five genes located on chromosome 6. These included gene 127136761 encoding squalene epoxidase; gene 127091639 encoding a transcription factor MYB SRM1; gene 127097033 encoding a 60S ribosomal protein L14; gene 127092211, encoding a BolA-like family protein, which, interestingly, was located within QTL BpLD.I, earlier described as conferring resistance to weevil in pea; and gene 127096593 encoding a methyltransferase. These associated genes offer valuable potential for developing pea varieties resistant to Bruchus spp. and efficient utilization of genomic resources through marker-assisted selection (MAS).

Identification of differentially expressed genes controlling the expression of flowering in Bambara groundnut (Vigna subterranea [L.] Verdc.)

Bambara groundnut flowering is a crucial developmental stage in the vegetative to reproductive period. The earliness to lateness of flowering is regulated by various interconnected genetic pathways encoded by genes. Deoxyribonucleic acid (DNA) of the selected accessions was extracted through leaf samples at 3 weeks old, using Dellaporta Miniprep for Plant DNA Isolation procedure. The high-quality DNA was sequenced using Diversity Arrays Technology (DArT) markers and single nucleotide polymorphisms (SNP’s) associated with flowering was identified. There is need to investigate the genetic make-up of the cleistogamous flower of Bambara through associated genes for improvement. This research work identified four markers associated with the flowering of Vigna subterranea and the role of variant identified genes in flowering. The identified markers from the sequence and the selected amino acid sequence were used as a query to search the legume protein database in Vigna radiata. The four markers with adequate information associated with flowering in the sequence were 24385352|F|0–28:T > C-28:T > C; 27641816|F|0–17:C > T-17:C > T; 24384204|F|0–24:C > T-24:C > T and 24346601|F|0–67:T > C-67:T > C and significant at P < 1.68 × 10−4 at chromosomes 7, 11, 4, and 5. The identified genes including histones, Polyketide, cyclase/dehydrase, Transcription factor MYC/MYB N-terminal, Rhamnogalacturonate lyase, DHHC-type zinc finger protein, Putative S-adenosyl-L-methionine-dependent methyltransferase, Ribosomal protein L2, D-galactoside/L-rhamnose binding SUEL lectin domain, Lipase GDSL, Histone deacetylase superfamily, Basic-leucine zipper domain, TUP1-like enhancer of split, Zinc finger ZZ-type, Homeodomain-like, Phosphatidylethanolamine-binding protein PEBP, Leucine-rich repeat which are tools in controlling flowering in Bambara groundnut. This study revealed that Bambara groundnut flowering is controlled by the interplay of genes.

Ribosome External Electric Field Regulates Metabolic Enzyme Activity: The RAMBO Effect.

Ribosomes bind to many metabolic enzymes and change their activity. A general mechanism for ribosome-mediated amplification of metabolic enzyme activity, RAMBO, was formulated and elucidated for the glycolytic enzyme triosephosphate isomerase, TPI. The RAMBO effect results from a ribosome-dependent electric field-substrate dipole interaction energy that can increase or decrease the ground state of the reactant and product to regulate catalytic rates. NMR spectroscopy was used to determine the interaction surface of TPI binding to ribosomes and to measure the corresponding kinetic rates in the absence and presence of intact ribosome particles. Chemical cross-linking and mass spectrometry revealed potential ribosomal protein binding partners of TPI. Structural results and related changes in TPI energetics and activity show that the interaction between TPI and ribosomal protein L11 mediate the RAMBO effect.

O-150 Identification and validation of RPL7 and RCCD1 as potential biomarkers associated with immune infiltration in patients with thin endometrium

Abstract Study question For patients with thin endometrium (TE), what potential genes could be utilized for exploring the underlying mechanisms and clinical therapy? Summary answer Ribosomal protein L7 (RPL7) and RCC1 domain containing 1 (RCCD1) were suggested as specific biomarkers for TE. What is known already TE is an important contributor to embryo implantation failure and female infertility. However, the pathogenesis and mechanism of TE are not clear, and consequently, there is a paucity of data on effective targeted treatments for patients with TE. Study design, size, duration Endometrial cells were collected from 18 women with TE and 18 normal controls for transcriptional sequencing. Experimental validation was based on other 10 endometrium samples, consisting of 6 TE samples and 4 controls. Participants/materials, setting, methods After performing transcriptional sequencing, differentially expressed genes (DEGs) were extracted between the two groups via bioinformatic analysis. Based on DEGs, we applied functional enrichment and LASSO analysis to identify potential biomarkers, whose expressions were then validated by quantitative real-time PCR and western blot. Immune infiltration as well as the correlation with immune cells was also explored in the study. Main results and the role of chance RPL7 and RCC1 were identified and validated to be potential biomarkers, which exhibited an overexpression in TE at both mRNA and protein levels. An abnormal immune environment was found in TE, and correlation analysis showed that the two candidate genes correlated with atypical regulation of immune cells. Limitations, reasons for caution It might not be adequate to evaluate TE by only considering the immunologic aspects. Moreover, prospective studies are required to determine whether RPL7 and RCC1 may be used for early clinical diagnosis and prediction of pregnancy outcomes. Wider implications of the findings Further understanding and better knowledge of the functions of RPL7 and RCCD1 can promote the development of targeted therapeutics to improve clinical outcomes of patients with TE. Trial registration number not applicable

Pan-cancer analysis of the prognostic and immunological role of RPL4

Ribosomal proteins (RPs) play an important role in the overall stability, function, and integrity of ribosomes. Ribosomal protein L4 (RPL4), which is encoded by RPL4, is assumed to play different roles in different cancers due to the strong correlation between them. However, research based on the underlying mechanisms of this correlations is limited. Therefore, this study investigated the biological role of RPL4 in various cancers. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to compare the differential expression of RPL4 in tumor and normal tissues. The Sangerbox database and Kaplan–Meier method were employed to assess RPL4's impact on the prognosis of pan-cancer. Analyses using the cBioPortal tool, Shiny Methylation Analysis Resource Tool (SMART), and MethSurv provided insights into the methylation and epigenetic alterations of RPL4. Gene enrichment analysis revealed that RPL4 is involved in ribosome biogenesis through multiple pathways, and its enrichment in signaling pathways directly or indirectly influence tumor development. Tumor Immune Single-cell Hub (TISCH) was used to analyze RPL4 expression levels and cellular functions in the tumor microenvironment. Tumor Immune Estimation Resource Database 2.0 (TIMER2.0) and Tumor-Immune System Interactions Database (TISIDB) tools revealed that RPL4 affected the immune infiltration potential of tumors. Furthermore, the application of the ROC mapper and CellMiner databases indicated an association between RPL4 and sensitivity to multiple antitumor drugs. Additionally, RPL4 was found to remodel the tumor immune microenvironment, leading to the development of chemoresistance. In conclusion, the findings suggest that RPL4 can be used as a potential tumor biomarker and may serve as a target for immunotherapy in various cancers. Genetic testing of RPL4 provides a foundation for the diagnosis, prognosis, and treatment of clinical tumors.

MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression.

Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non-small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear. The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for invivo analysis. MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. Invitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth invivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells invitro and invivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells. MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism invitro and impeded tumor growth invivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.

Ribosomal Protein L9 Maintains Stemness of Colorectal Cancer via an ID-1 Dependent Mechanism.

The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133+ cancer stem cells (CSCs) were then separated from CD133- cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133+ colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133+ HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.

ZBTB7A interferes with the RPL5-P53 feedback loop and reduces endoplasmic reticulum stress-induced apoptosis of pancreatic cancer cells.

Endoplasmic reticulum (ER) stress is a primary mechanism leading to cell apoptosis, making it of great research interests in cancer management. This study delves into the function of ribosomal protein L5 (RPL5) in ER stress within pancreatic cancer (PCa) cells and investigates its regulatory mechanisms. Bioinformatics predictions pinpointed RPL5 as an ER stress-related gene exhibiting diminished expression in PCa. Indeed, RPL5 was found to be poorly expressed in PCa tissues and cells, with this reduced expression correlating with an unfavorable prognosis. Moreover, RPL5 overexpression led to heightened levels of p-PERK, p-eIF2α, and CHOP, bolstering the proapoptotic effect of Tunicamycin, an ER stress activator, on PCa cells. Additionally, the RPL5 overexpression curbed cell proliferation, migration, and invasion. Tunicamycin enhanced the binding between RPL5 and murine double minute 2 (MDM2), thus suppressing MDM2-mediated ubiquitination and degradation of P53. Consequently, P53 augmentation intensified ER stress, which further enhanced the binding between RPL5 and MDM2 through PERK-dependent eIF2α phosphorylation, thereby establishing a positive feedback loop. Zinc finger and BTB domain containing 7A (ZBTB7A), conspicuously overexpressed in PCa samples, repressed RPL5 transcription, thereby reducing P53 expression. Silencing of ZBTB7A heightened ER stress and subdued the malignant attributes of PCa cells, effects counteracted upon RPL5 silencing. Analogous outcomes were recapitulated in vivo employing a xenograft tumor mouse model, where ZBTB7A silencing dampened the tumorigenic potential of PCa cells, an effect reversed by additional RPL5 silencing. In conclusion, this study suggests that ZBTB7A represses RPL5 transcription, thus impeding the RPL5-P53 feedback loop and mitigating ER-induced apoptosis in PCa cells.

Epstein-Barr virus noncoding RNA EBER1 promotes the expression of a ribosomal protein paralog to boost oxidative phosphorylation.

Epstein-Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV-encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22-like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1-containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.

Screening of reference genes for gene expression study in different tissues from the transcriptome data of the vector leafhopper Psammotettix striatus

Selecting appropriate reference genes is crucial for ensuring the accuracy and reliability of gene expression study using reverse transcription-quantitative PCR (RT-qPCR). To screen the optimal reference genes for analyzing gene expression in different tissues of the vector leafhopper Psammotettix striatus which causes extensive damage to a wide range of crops by vectoring multiple plant pathogenic microorganisms, the transcriptome data from Malpighian tubules (MTs) of P. striatus were mined. Twenty alternative candidate reference genes were initially selected for screening, among which seven genes with diverse Gene Ontology (GO) annotations were choosed as candidate reference genes, i.e., ribosomal protein L7A (RPL7A), ribosomal protein S28 (RPS28), ribosomal protein L22 (RPL22), ribosomal protein LP2 (RPLP2), H3 histone family 3A (H3F3A), elongation factor 1γ (EF-1γ), and elongation factor 1α (EF-1α). Gene expression levels in different tissues of P. striatus adults were examined using RT-qPCR, and their expression stability was analyzed using multiple reference gene screening software. This study revealed EF-1α as the most abundantly expressed gene, while RPL22 exhibited the lowest expression levels. EF-1α showed the most stable expression, whereas RPS28 showed the least stability. Various software tools confirmed EF-1α as the most stable single reference gene, and EF-1α and RPLP2 an optimal combination. This study provides a foundation for future investigation of the transmission of pathogenic microorganisms mediated by the vector leafhoppers, the function of the MTs, the biosynthesis of brochosomes, the coevolutionary processes and nutritional interactions of symbionts and host insects, and the gene expression study of other sap-sucking insects.

Endoplasmic reticulum stress-related gene expression patterns in glioblastoma models identified by single-cell RNA sequencing: Implications for prognosis and treatment

Objective: Endoplasmic reticulum (ER) stress has therapeutic potential for a variety of malignancies, including glioma. In this study, bioinformatics was used to analyze ER stress-related genes (ERGs) in glioblastoma (GBM), explore their functions and pathways, construct prognostic models, and explore new treatment strategies. Methods: Various bioinformatics algorithms were utilized to screen for ERGs and construct a risk model. According to the expression of ERGs, different subtypes were classified using the consensus clustering method. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were performed on the subtypes. Based on screened risk genes, GBM patients were divided into Train and Test groups in a 1:1 ratio. The prognostic model was validated through Receiver Operating Characteristic (ROC) curve analysis and independent prognostic analysis. The model was further validated by comparing the risk scores between high-risk and low-risk groups, and comparisons were made in terms of survival time, immune microenvironment, and pathway regulation. Drug sensitivity was used to screen drugs for low- and high- risk group, and single-cell RNA sequencing (scRNA-seq) analysis were utilized to explore the expression distribution of risk genes in GBM. Results: According to the ERGs, GBM samples can be divided into two groups with significant differences. Cluster A showed better survival rates compared to Cluster B. GSVA and GSEA analysis revealed that Cluster A was mainly enriched in glutamate receptor signaling pathway, synaptic transmission between neurons, postsynaptic density membrane, postsynaptic membrane, and synaptic vesicle membrane functions. It is worth noting that 8 ERGs were screened as model genes, which can effectively and independently predicate the survival risk of GBM patients with high accuracy and discrimination ability. Subsequently, changes in immune cell populations were observed in high-risk and low-risk groups, with differences in memory B cells and resting CD4 memory T cells between the high-risk and low-risk groups. The high-risk group had higher levels of memory B cells, while the low-risk group had higher levels of resting CD4 memory T cells. Furthermore, potential therapeutic strategies were identified, with BI-2536, Daporinad, SB505124, UMI-77, and Vorinostat identified for the low-risk group, while AZD8055, Camptothecin, Gemcitabine, PD0325901, and Topotecan identified for the high-risk group. scRNA-seq identified Ribosomal Protein L10 (RPL10) as one of the eight ER stress-related genes, primarily expressed in malignant cells of various tumors. Conclusion: This study identified eight ERGs and constructed a risk model based on bioinformatics analysis, which can be used for prognosis prediction and drug screening.

Nascent chains derived from a foldable protein sequence interact with specific ribosomal surface sites near the exit tunnel

In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp1–140 interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63–94 residues. Longer RNCs (apoHmp1–189) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.

Bombyx mori RPL13 participates in UV-induced DNA damage repair of B. mori nucleopolyhedrovirus through interaction with Bm65.

Ribosomal protein L13 (RPL13) is highly conserved in evolution. At present, the properties and functions of RPL13 have not been characterised in insects. In this study, Bombyx mori RPL13 (BmRPL13) was first found to be specifically recruited to the sites of ultraviolet (UV)-induced DNA damage and contributed to UV damage repair. Escherichia coli expressing BmRPL13 showed better resistance to UV radiation. After knocking down the expression of BmRPL13 in BmN cells, the repair speed of UV-damaged DNA slowed down. The further results showed that BmRPL13 interacted with B. mori nucleopolyhedrovirus (BmNPV) ORF65 (Bm65) protein to locate at the UV-induced DNA damage sites of BmNPV and helped repair UV-damaged viral DNA.

Identification of Mycobacterium abscessus using the peaks of ribosomal protein L29, L30 and hemophore-related protein by MALDI-MS proteotyping

Mycobacteroides (Mycobacterium) abscessus, which causes a variety of infectious diseases in humans, is becoming detected more frequently in clinical specimens as cases are spreading worldwide. Taxonomically, M. abscessus is composed of three subspecies of M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense, with different susceptibilities to macrolides. In order to identify rapidly these three subspecies, we determined useful biomarker proteins, including ribosomal protein L29, L30, and hemophore-related protein, for distinguishing the subspecies of M. abscessus using the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) profiles. Thirty-three clinical strains of M. abscessus were correctly identified at the subspecies-level by the three biomarker protein peaks. This study ultimately demonstrates the potential of routine MALDI-MS-based laboratory methods for early identification and treatment for M. abscessus infections.

Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China

BackgroundRecently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important.MethodsThe antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR.ResultsAll the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates.ConclusionThe emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

Oncogenic role of RNA-binding protein GNL2 in glioma: Promotion of tumor development through enhancing protein synthesis.

RNA-binding proteins (RBPs) are aberrantly expressed in various diseases, including glioma. In the present study, the role and mechanism of RBPs in glioma were investigated. Differentially expressed genes (DEGs) in glioma were screened from public databases and overlapping genes between DEGs and RBPs were selected in a bioinformatics analysis to identify the hub gene. Next, evaluation of expression, survival analysis and cell experiments were performed to examine the impact of the hub gene on glioma. Through bioinformatics analysis, G protein nucleolar 2 (GNL2), programmed cell death 11 (PDCD11) and ribosomal protein S6 (RPS6) were identified as potential biomarkers in glioma prognosis and GNL2 was chosen as the hub gene for further investigation. GNL2 was increased in glioma tissues and related to poor survival outcomes. Cell experiments revealed that GNL2 knockdown inhibited glioma cell growth, migration and invasion. In addition, GNL2 was found to affect the overall protein synthesis of ribosomal protein L11 in glioma cells. In conclusion, GNL2, PDCD11 and RPS6 may serve as potential biomarkers in glioma prognosis. Importantly, GNL2 acts as an oncogene in glioma and it enhances protein synthesis to promote the development of brain glioma.