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Pivotal role of mTORC2 and involvement of ribosomal protein S6 in cardioprotective signaling.

RATIONALE: There is tight coupling between Akt activation and suppression of cell death. Full Akt activation requires mammalian target of rapamycin complex 2 (mTORC2), but the regulation of mTORC2 is unclear. OBJECTIVE: To gain new insights into mechanisms of mTORC2/Akt signaling. METHODS AND RESULTS: The role of mTORC2 in cardioprotection was examined. In perfused mouse hearts, ischemic preconditioning increased mTORC2 activity, leading to phosphorylation of Akt on Ser473. The protective effect of ischemic preconditioning was lost by pretreatment with dual mTORC inhibitors but not with rapa

Human recombinant antibodies against Trypanosoma cruzi ribosomal P2β protein.

Patients with chronic Chagas' Heart Disease (cChHD) develop an antibody response that is suspected to be involved in the cardiac pathogenesis. The response against Trypanosoma cruzi ribosomal P proteins is of particular interest, as these antibodies can cross-react with host cardiac receptors causing electrophysiological alterations. To better understand the humoral anti-P response we constructed a single-chain variable fragment library derived from a cChHD patient. The variable heavy and light regions were amplified from bone-marrow RNA and subcloned into the vector pComb3X. The phage library

Ribosomal protein L11 mutation in zebrafish leads to haematopoietic and metabolic defects.

Mutations in ribosomal proteins are associated with a congenital syndrome, Diamond-Blackfan anaemia (DBA), manifested by red blood cell aplasia, developmental abnormalities and increased risk of malignancy. Recent studies suggest the involvement of p53 activation in DBA. However, which pathways are involved and how they contribute to the DBA phenotype remains unknown. Here we show that a zebrafish mutant for the rpl11 gene had defects both in the development of haematopoietic stem cells (HSCs) and maintenance of erythroid cells. The molecular signature of the mutant included upregulation of p5…

Autoantibody against ribosomal protein L14 in patients with systemic lupus erythematosus.

OBJECTIVE: To isolate a specific antibody against ribosomal protein L14 and to assess the relationship of this antibody with some of the clinicalfeatures in patients with systemic lupus erythematosus (SLE). METHODS: We screened the sera of SLE patients by immunoblotting analysis using rat total ribosomal proteins as antigen to determine whether sera had antibody activity against ribosomal proteins other than the P S10, and L12 proteins. The sera from 2 patients had antibody activity against a 30-kDa ribosomal protein. This antigenic protein was identified to be ribosomal protein L14 by two-di…

SGIV and RGNNV regulate fish innate immune responses by mediating ubiquitinated modifications of proteasome and ribosomal proteins.

Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) have been identified as the predominant DNA and RNA viral pathogens, respectively, affecting grouper populations. Protein ubiquitination, a crucial post-translational modification, plays pivotal regulatory roles in both host innate immune responses and viral replication processes. In the present study, we employed quantitative proteomics approaches to systematically identify and characterize alterations in ubiquitination-modified proteins in grouper spleen (Epinephelus akaara, GS) cells following SGIV an

The RNA-dependent RNA polymerase of enterovirus A71 associates with ribosomal proteins and positively regulates protein translation.

Enteroviruses, which may cause neurological complications, have become a public health threat worldwide in recent years. Interactions betwee … e 3D protein interacts with factors involved in translation-related biological processes, including ribosomal proteins. In addition, polysome profiling analysis showed that the 3D protein cosediments with small and large subunits of ribosomes. We further discovered that the EV-A71 3D protein could enhance EV-A71 internal ribosome entry site (IRES)-dependent translat …

A simple, rapid typing method for Streptococcus agalactiae based on ribosomal subunit proteins by MALDI-TOF MS.

Streptococcus agalactiae (Group B Streptococcus, GBS), is a frequent human colonizer and a leading cause of neonatal meningitis as well as an emerging pathogen in non-pregnant adults. GBS possesses a broad animal host spectrum, and recent studies proved atypical GBS genotypes can cause human invasive diseases through animal sources as food-borne zoonotic infections. We applied a MALDI-TOF MS typing method, based on molecular weight variations of predefined 28 ribosomal subunit proteins (rsp) to classify GBS strains of varying serotypes into major phylogenetic lineages. A total of 249 GBS isola

Characterization of the human autoimmune response to the major C-terminal epitope of the ribosomal P proteins.

Autoantibodies to the ribosomal phospho (-P) proteins P0, P1, and P2, collectively referred to as Rib-P, are specifically found in 10-40% of patients with systemic lupus erythematosus (SLE). These antibodies are believed to be correlated with lupus nephritis, hepatitis, and central nervous system involvement. The major immunoreactive epitope of these ribosomal antigens has been localized to the carboxy terminus, which is a highly conserved domain of all three proteins and contains two phosphorylated serine residues. The phosphorylated amino acids of the P proteins are known not to be critical

Convergent nuclear proteostasis alterations across 40S ribosomal protein deficiencies.

Defects in ribosome biogenesis cause ribosomopathies, but the pathogenic role of malformed preribosomes remains unclear. Using preribosome fractionation, live-cell and confocal microscopy, and automated imaging screens, we tracked abortive preribosomes following depletion of the 33 small-subunit ribosomal proteins (RPSs). We found that all RPS deficiencies lead to accumulation of nucleolar preribosome materials in the nucleoplasm, regardless of the affected 40S subunit maturation stage. These aberrant particles appear as dispersed complexes or persistent aggregates arising during nucleolar rea…

The ribosome-inactivating proteins MAP30 and Momordin inhibit SARS-CoV-2.

The continuing emergence of SARS-CoV-2 variants has highlighted the need to identify additional points for viral inhibition. Ribosome inactivating proteins (RIPs), such as MAP30 and Momordin which are derived from bitter melon (Momordica charantia), have been found to inhibit a broad range of viruses. MAP30 has been shown to potently inhibit HIV-1 with minimal cytotoxicity. Here we show that MAP30 and Momordin potently inhibit SARS-CoV-2 replication in A549 human lung cells (IC50 ~ 0.2 μM) with little concomitant cytotoxicity (CC50 ~ 2 μM). Both viral inhibition and cytotoxicity remain unalter

[Syndromic growth retardation caused by impaired function of the ribosomal protein eL13].

Growth retardation for more than 2 SD below the average population or presumed familial target height is classified as a short stature and may be a clinical manifestation of a large number of disorders. The use of the latest methods of molecular genetic analysis in recent years has allowed for a better understanding of the pathogenesis of inherited forms of a short stature. One of the recently discovered mechanisms of this pathology was monoallelic mutations in RPL13 gene, leading to the development of Isidor-Toutain type spondyloepimetaphyseal dysplasia (SEDM). Characteristic phenotypic featu

Ребосомный белок RACK1 способствует переводу полиомиелитвируса и других вирусных IRES.

Вирусы разработали стратегии для обеспечения эффективного перевода с использованием хостинговых лент и факторов перевода. Помимо детонирующих факторов начала перевода, требуемых для перевода в принимающих камерах, полиомиелитвирус (PV) использует внутренний рибосомный вход (IRES). Недавние исследования показывают, что вирусы используют конкретные рибосомные белки для улучшения перевода своих вирусных белков. Реберосомный белковый рецептор активированной C cinase 1 (RACK1), белок рибосомальной субединицы 40S, ранее был продемонстрирован как посредник в переводе с 5-ти крикетного паралича и виру

Совпадение в аннотации оригинала
Viruses have evolved strategies to ensure efficient translation using host cell ribosomes and translation factors. In addition to cleaving translation initiation factors required for host cell translation, poliovirus (PV) uses an internal ribosome entry site (IRES). Recent studies suggest that viruses exploit specific ribosomal proteins to enhance translatio…

Autophagic flux is required for the synthesis of triacylglycerols and ribosomal protein turnover in Chlamydomonas.

Autophagy is an intracellular catabolic process that allows cells to recycle unneeded or damaged material to maintain cellular homeostasis. … sphate-starved cells. Moreover, we found that concanamycin A treatment prevented the degradation of ribosomal proteins RPS6 and RPL37 under nitrogen or phosphate deprivation. These results indicate that autophagy might play an important role in the regulation of lipid metabolism and the recycling of ribosomal proteins under nutrient limitation in Chlamydomonas.

Dosage Sensitivity of RPL9 and Concerted Evolution of Ribosomal Protein Genes in Plants.

The ribosome in higher eukaryotes is a large macromolecular complex composed of four rRNAs and eighty different ribosomal proteins. In plants, each ribosomal protein is encoded by multiple genes. Duplicate genes within a family are often necessary to provide a threshold dose of a ribosomal protein but in some instances appear to have non-redundant functions. Here, we addressed whether divergent members of the RPL9 gene family are dosage sensitive or whether these genes have non-overlapping functions. The RPL9 family in Arabidopsis thaliana comprises two nearly identical members, RPL9B and RPL9…

A Case of Diamond Blackfan Anemia (DBA) with Mutation in Ribosomal Protein S19.

Diamond Blackfan Anemia (DBA) is a rare disorder which presents with anemia in early infancy. This disorder is genetically and clinically heterogeneous in nature. The inheritance is mainly autosomal dominant. Approximately 25% of the cases are associated with craniofacial anomalies and some cases may end up in malignancy. The diagnosis is made by blood investigations, and bone marrow studies in which red cell precursors are reduced or absent. Screening for the mutations including those encoding for ribosomal proteins in the patient and the family members confirms the diagnosis. Human Leukocyte…

RNA-protein distance patterns in ribosomes reveal the mechanism of translational attenuation.

Elucidating protein translational regulation is crucial for understanding cellular function and drug development. A key molecule in protein translation is ribosome, which is a super-molecular complex extensively studied for more than a half century. The structure and dynamics of ribosome complexes were resolved recently thanks to the development of X-ray crystallography, Cryo-EM, and single molecule biophysics. Current studies of the ribosome have shown multiple functional states, each with a unique conformation. In this study, we analyzed the RNA-protein distances of ribosome (2.5 MDa) comple

Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae.

Spectinomycin remains a useful reserve option for therapy of gonorrhea. The emergence of multidrug-resistant Neisseria gonorrhoeae strains with decreased susceptibility to cefixime and to ceftriaxone makes it the only medicine still effective for treatment of gonorrhea infection in analogous cases. However, adoption of spectinomycin as a routinely used drug of choice was soon followed by reports of spectinomycin resistance. The main molecular mechanism of spectinomycin resistance in N. gonorrhoeae was C1192T substitution in 16S rRNA genes. Here we reported a Thr-24→Pro mutation in ribosomal pr

Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation.

Three patients born to the same set of consanguineous parents presented with antenatal skin oedema, hypotonia, cardiomyopathy and tubulopathy. The enzymatic activities of multiple mitochondrial respiratory chain complexes were reduced in muscle. Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts. Homozygosity mapping led to the identification of a mutation in the MRPS22 gene, which encodes a mitochondrial ribosomal protein. Transfection of the patient cells with wild-type MRPS22 cDNA increased the 12s rRNA content and normalised the en

Molecular and immunological characterization of L14 ribosomal protein from Leishmania braziliensis.

The isolation and molecular characterization of the gene coding for L14 ribosomal protein from L. braziliensis is described. There are 2 cop … m trypanosomatids and approximately 25% with its counterparts from higher eukaryotic organisms. L14 ribosomal proteins from trypanosomatids and higher eukaryotes share along their molecules a similar distribution pattern of theoretically functional domains. L. braziliensis L14 recombinant protein is not recognized by sera from cutaneous leishmaniasis patients. Immun …

Regulated phosphorylation of 40S ribosomal protein S6 in root tips of maize.

Ribosomal protein S6 (RPS6) is located in the mRNA binding site of the 40S subunit of cytosolic ribosomes. Two maize (Zea mays) rps6 genes were identified that encode polypeptides (30 kD, 11.4 pI) with strong primary amino acid sequence and predicted secondary structure similarity to RPS6 of other eukaryotes. Maize RPS6 was analyzed by the use of two-dimensional gel electrophoresis systems, in vivo labeling with [(32)P]P(i) and immunological detection. Nine RPS6 isoforms were resolved in a two-dimensional basic-urea/sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. Matrix-assis