Extra-ribosomal Functions Research Articles

The Interplay Between the MYC Oncogene and Ribosomal Proteins in Osteosarcoma Onset and Progression: Potential Mechanisms and Indication of Candidate Therapeutic Targets.

High-grade osteosarcoma (OS) is the most common primary bone tumor mainly affecting children and young adults. First-line treatment consists of neo-adjuvant chemotherapy with doxorubicin, cisplatin, and methotrexate and surgery. The mean long-term survival rate for localized disease at diagnosis is 65-70%, dropping down to 20% when metastases are present at diagnosis. Therefore, curing OS is a clinical challenge, particularly for patients that do not respond to standard treatments. MYC has frequently been reported to be involved in the pathogenesis of OS and its high expression may be associated with drug resistance and patients' worse prognosis. Moreover, MYC is a master regulator of ribosomal proteins (RPs) synthesis and ribosome biogenesis (RiBi), which is often up-regulated in human tumors. In recent years, RPs have been recognized not only for their traditional role in ribosome assembly but also for their extra-ribosomal functions, many of which are linked to the onset and progression of cancer. In this review we focus on the role and possible interplay of MYC and RPs expression in association with drug resistance and worse prognosis in OS and discuss therapeutic options that target de-regulated MYC, RiBi, or RPs, which are already clinically available or under evaluation in clinical trials.

Ribosomal proteins: the missing piece in the inflammation puzzle?

Ribosomal proteins (RPs) are constituents of macromolecular machinery, ribosome that translates genetic information into proteins. Besides ribosomal functions, RPs are now getting appreciated for their 'moonlighting'/extra-ribosomal functions modulating many cellular processes. Accumulating evidence suggests that a number of RPs are involved in inflammation. Though acute inflammation is a part of the innate immune response, uncontrolled inflammation is a driving factor for several chronic inflammatory diseases. An in-depth understanding of inflammation regulation has always been valued for the better management of associated diseases. Hence, this review first outlines the common livelihood of RPs and then provides a comprehensive account of five RPs that significantly contribute to the inflammation process. Finally, we discuss the possible therapeutic uses of RPs against chronic inflammatory diseases.

CDNA characterization of the ribosomal protein L10a gene and its functional analysis in ovarian development of Macrobrachium nipponense

Ribosomal proteins (RPs) not only play an important role in protein synthesis but also have extraribosomal functions. In this study, the entire cDNA sequence of the RPL10a gene of Macrobrachium nipponense (MnRPL10a) was cloned by RACE-PCR. The obtained complete cDNA sequence of the MnRPL10a gene was 885 bp encoding 217 amino acids (AAs). The expression pattern of the MnRPL10a gene was analysed by quantitative real-time fluorescence PCR (qPCR), and its mRNA location was determined by fluorescence in situ hybridization (FISH). The results showed that during development, the highest expression of MnRPL10a in the fertilized ovum. Among tissues, it was mostly expressed in the ovary, and its highest expression was found in stage V ovaries. MnRPL10a mRNA was mainly distributed in the cytoplasm of oogonia and oocytes. The role of the MnRPL10a gene in ovarian development was verified by RNA interference (RNAi) and ovarian explant incubation with 5-hydroxytryptamine (5-HT) and dopamine (DA) experiments. The results indicated that the expression of the genes that positively regulate ovarian development, including vitellogenin (Vg), vitellogenin receptor (Vgr), cell cycle protein B (CyclinB) and cell division cyclin 2 (cdc2), decreased, while the expression of the genes that negatively regulate ovarian development, including Wee1 kinase (Wee1) and OTU domain-containing ubiquitin aldehyde-binding protein B (OTUB), increased with the decrease in MnRPL10a expression after RNAi and DA incubation. However, 5-HT incubation showed the opposite results. In summary, the MnRPL10a gene may regulate the development of the ovary in M. nipponense by affecting vitellin synthesis, oocyte meiosis and the oestrogen signalling pathway.

Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13

Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2–64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, retaining the same radiographic pattern of spondylar- and epi-metaphyseal dysplasia, but with varying severity of the hip and knee deformities. Two new missense variants, c.548 G>A, p.(Arg183His) and c.569 G>T, p.(Arg190Leu), and a previously known splice variant c.477+1G>A were identified, confirming mutational clustering in a highly specific RNA binding motif. Structural analysis and interpretation of the variants’ impact on the protein suggests that disruption of extra-ribosomal functions of the protein through binding of mRNA may play a role in the skeletal phenotype of SEMD-RPL13. In addition, we present gonadal and somatic mosaicism for the condition.

Molecular and functional characterization of ribosome protein S24 in ovarian development of Macrobrachium nipponense

Ribosomal proteins (RPs) have mang extraribosomal functions including regulation of ovarian development in some organisms. In order to solve the problem of rapid ovarian maturation in Macrobrachium nipponense aquaculture, this study identified a RPS24 (MnRPS24) gene from M. nipponense, which encodes a protein of ββαβαααα folding structure type. MnRPS24 exhibited the greatest expressions in the female adult stage among the six growth stages, in the ovary among the nine tissues, and in the stage I ovary among the six ovarian development stages. The MnRPS24 protein located in the cytoplasm of oogonia, previtellogenic and early-vitellogenic oocytes, and the follicular cells surrounding the oocytes. The expression of the vitellogenin (MnVg), vitellogenin receptor (MnVgr), cell cycle protein B (MnCyclin B) and cell division cyclin 2 (MnCdc2) genes were increased by recombinant MnRPS24 protein incubation. Conversely, the expression of the Wee1 kinase (MnWee1) gene was decreased. MnRPS24 gene silencing downregulated the expression for MnVg, MnVgr, MnCyclin B and MnCdc2 and upregulated the expression for MnWee1. Furthermore, MnRPS24 gene silencing delayed the vitellogenesis of oocytes, halting the progression of ovarian development. The findings of this research demonstrate that MnRPS24 could potentially function as a stimulator in promoting the development of ovaries in M. nipponense.

Loss of function of ribosomal protein L13a blocks blastocyst formation and reveals a potential nuclear role in gene expression.

Ribosomal proteins play diverse roles in development and disease. Most ribosomal proteins have canonical roles in protein synthesis, while some exhibit extra-ribosomal functions. Previous studies in our laboratory revealed that ribosomal protein L13a (RPL13a) is involved in the translational silencing of a cohort of inflammatory proteins in myeloid cells. This prompted us to investigate the role of RPL13a in embryonic development. Here we report that RPL13a is required for early development in mice. Crosses between Rpl13a+/- mice resulted in no Rpl13a-/- offspring. Closer examination revealed that Rpl13a-/- embryos were arrested at the morula stage during preimplantation development. RNA sequencing analysis of Rpl13a-/- morulae revealed widespread alterations in gene expression, including but not limited to several genes encoding proteins involved in the inflammatory response, embryogenesis, oocyte maturation, stemness, and pluripotency. Exvivo analysis revealed that RPL13a was localized to the cytoplasm and nucleus between the two-cell and morula stages. RNAi-mediated depletion of RPL13a phenocopied Rpl13a-/- embryos and knockdown embryos exhibited increased expression of IL-7 and IL-17 and decreased expression of the lineage specifier genes Sox2, Pou5f1, and Cdx2. Lastly, a protein-protein interaction assay revealed that RPL13a is associated with chromatin, suggesting an extra ribosomal function in transcription. In summary, our data demonstrate that RPL13a is essential for the completion of preimplantation embryo development. The mechanistic basis of the absence of RPL13a-mediated embryonic lethality will be addressed in the future through follow-up studies on ribosome biogenesis, global protein synthesis, and identification of RPL13a target genes using chromatin immunoprecipitation and RNA-immunoprecipitation-based sequencing.

Ribosomal protein L8 regulates the expression and splicing pattern of genes associated with cancer-related pathways.

Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. RPL8-OE inhibited cell proliferation and promoted cell apoptosis. RPL8 regulated the differential expression of many oncogenic genes and the occurrence of RASEs. Many DEGs and RASE genes (RASGs) were enriched in tumorigenesis and tumor progression-related pathways, including angiogenesis, inflammation, and regulation of cell proliferation. RPL8 could regulate the RASGs enriched in the negative regulation of apoptosis, consistent with its proapoptosis function. Furthermore, RPL8 may influence cancer-related DEGs by modulating the alternative splicing of transcription factors. RPL8 might affect the phenotypes of cancer cells by altering the transcriptome profiles, including gene expression and splicing, which provides novel insights into the biological functions of RPL8 in tumor development.

Two "Edges" in Our Knowledge on the Functions of Ribosomal Proteins: The Revealed Contributions of Their Regions to Translation Mechanisms and the Issues of Their Extracellular Transport by Exosomes.

Ribosomal proteins (RPs), the constituents of the ribosome, belong to the most abundant proteins in the cell. A highly coordinated network of interactions implicating RPs and ribosomal RNAs (rRNAs) forms the functionally competent structure of the ribosome, enabling it to perform translation, the synthesis of polypeptide chain on the messenger RNA (mRNA) template. Several RPs contact ribosomal ligands, namely, those with transfer RNAs (tRNAs), mRNA or translation factors in the course of translation, and the contribution of a number of these particular contacts to the translation process has recently been established. Many ribosomal proteins also have various extra-ribosomal functions unrelated to translation. The least-understood and -discussed functions of RPs are those related to their participation in the intercellular communication via extracellular vesicles including exosomes, etc., which often carry RPs as passengers. Recently reported data show that such a kind of communication can reprogram a receptor cell and change its phenotype, which is associated with cancer progression and metastasis. Here, we review the state-of-art ideas on the implications of specific amino acid residues of RPs in the particular stages of the translation process in higher eukaryotes and currently available data on the transport of RPs by extracellular vesicles and its biological effects.

Ribosomal Protein uS5 and Friends: Protein-Protein Interactions Involved in Ribosome Assembly and Beyond.

Ribosomal proteins are fundamental components of the ribosomes in all living cells. The ribosomal protein uS5 (Rps2) is a stable component of the small ribosomal subunit within all three domains of life. In addition to its interactions with proximal ribosomal proteins and rRNA inside the ribosome, uS5 has a surprisingly complex network of evolutionarily conserved non-ribosome-associated proteins. In this review, we focus on a set of four conserved uS5-associated proteins: the protein arginine methyltransferase 3 (PRMT3), the programmed cell death 2 (PDCD2) and its PDCD2-like (PDCD2L) paralog, and the zinc finger protein, ZNF277. We discuss recent work that presents PDCD2 and homologs as a dedicated uS5 chaperone and PDCD2L as a potential adaptor protein for the nuclear export of pre-40S subunits. Although the functional significance of the PRMT3-uS5 and ZNF277-uS5 interactions remain elusive, we reflect on the potential roles of uS5 arginine methylation by PRMT3 and on data indicating that ZNF277 and PRMT3 compete for uS5 binding. Together, these discussions highlight the complex and conserved regulatory network responsible for monitoring the availability and the folding of uS5 for the formation of 40S ribosomal subunits and/or the role of uS5 in potential extra-ribosomal functions.

Roles of ribosomal proteins in hematologic disorders and cancers: a review

Abstract Ribosomes are important organelles for synthesizing proteins in cells. They are composed of ribosomal RNA and more than 80 ribosomal proteins. It is well known that an essential function of ribosomal proteins is to participate in protein translation. In addition, ribosomal proteins also perform extra-ribosomal functions, such as participating in DNA replication, transcription, and damage repair, regulating cell growth, proliferation, apoptosis, and transformation. In recent years, studies have shown that alterations in ribosomal protein synthesis or function can lead to various hematologic diseases, including Diamond-Blackfan anemia, 5q-syndrome, Shwachman-Diamond syndrome, and other blood system diseases. Moreover, abnormal expressions of specific ribosomal protein genes have been reported in many malignant tumors. In this review, we elaborated on the changes in ribosomal proteins in hepatocellular carcinoma and colorectal, prostate, gastric, esophageal, and other cancers and discussed the relationship between ribosomal proteins and the occurrence of hematologic disorders and cancers.

Ribosomes and Ribosomal Proteins Promote Plasticity and Stemness Induction in Glioma Cells via Reprogramming.

Glioblastoma multiforme (GBM) is a lethal tumor that develops in the adult brain. Despite advances in therapeutic strategies related to surgical resection and chemo-radiotherapy, the overall survival of patients with GBM remains unsatisfactory. Genetic research on mutation, amplification, and deletion in GBM cells is important for understanding the biological aggressiveness, diagnosis, and prognosis of GBM. However, the efficacy of drugs targeting the genetic abnormalities in GBM cells is limited. Investigating special microenvironments that induce chemo-radioresistance in GBM cells is critical to improving the survival and quality of life of patients with GBM. GBM cells acquire and maintain stem-cell-like characteristics via their intrinsic potential and extrinsic factors from their special microenvironments. The acquisition of stem-cell-like phenotypes and aggressiveness may be referred to as a reprogramming of GBM cells. In addition to protein synthesis, deregulation of ribosome biogenesis is linked to several diseases including cancer. Ribosomal proteins possess both tumor-promotive and -suppressive functions as extra-ribosomal functions. Incorporation of ribosomes and overexpression of ribosomal protein S6 reprogram and induce stem-cell-like phenotypes in GBM cells. Herein, we review recent literature and our published data on the acquisition of aggressiveness by GBM and discuss therapeutic options through reprogramming.

PRRSV Induces HMGB1 Phosphorylation at Threonine-51 Residue to Enhance Its Secretion.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.

Ribosomal Proteins and Cancer

The translation process consists of translation factors and ribosomes. Ribosomal components include ribosomal proteins (RP) and ribosomal RNA. Many RPs are involved in assembling ribosomal particles and or stabilizing important regions of rRNA. Besides their conventional roles, RPs have been reported to exhibit secondary functions that have not yet been fully characterized in other cellular processes such as DNA repair, apoptosis, drug resistance, proliferation, and growth inhibition. Since cancer cells require a large amount of protein, they need ribosomes that work much more efficiently than normal cells. Several tumor suppressors and oncogenic proteins control the progression of cancer cells by regulating ribosome biogenesis and protein synthesis. Interestingly, free RPs also have diverse roles in tumorigenesis or tumor suppression. The physiological link between RPs and cancers has been extensively reviewed and elucidated on several pathways, including their interaction with the p53-MDM2 complex. The first evidence of an association between RPs and cancer came from observing the haploinsufficiency of eS4 in Turner Syndrome and eS19 mutation in Diamond-Blackfan Anemia. In the following years, the roles of different RPs in various cancer types such as colorectal cancer, breast cancer, lung adenocarcinoma, T-cell acute lymphoblastic leukemia, prostate cancer, breast cancer, gastric carcinomas, ovarian cancer, and liver cancer have been the subject of research. Apart from their effects on carcinogenesis, it was also emphasized that RPs could be evaluated as predictive biomarkers for diagnosis, prognosis, and treatment for some cancer types. In addition, some studies have been conducted on the use of these proteins in cancer treatment. Identifying novel extra-ribosomal functions of some RPs has identified these proteins as a new class of oncogenic or tumor suppressor factors. Suppression and stimulation of the expression of these novel oncogenic and tumor suppressor proteins, respectively, are considered could open up new therapeutic strategies in cancer therapy.

Identification of ribosomal protein L24 (RPL24) from the oriental river prawn, Macrobrachium nipponense, and its roles in ovarian development

Ribosomal proteins exhibit various extraribosomal functions in addition to their roles in protein synthesis. In this study, complementary DNA (cDNA) of ribosomal protein L24 in Macrobrachium nipponense (MnRPL24) was isolated, and its role in ovarian development was investigated using quantitative real-time PCR (qPCR), immunohistochemistry (IHC), RNA interference (RNAi) and histological observations. The complete cDNA of MnRPL24 is 564 base pairs (bps) and contains a 486 bp open reading frame (ORF) encoding 162 amino acids (aas). The highest expression level of MnRPL24 among eight tissues was found in the ovary, specifically in the stage I ovary. The MnRPL24 protein existed in the cytoplasm and nucleus of developing oocytes, and also existed in the cytoplasm of follicle cells in developing ovaries. After MnRPL24 knockdown by RNAi, the expression levels of vitellogenin (Vg), vitellogenin receptor (Vgr), cyclin-dependent kinase 2 (Cdc2) and M-phase cyclin (Cyclin B) genes and the gonadsomatic index (GSI) did not show the typical trend of gradually elevation with ovarian development and finally decrease in the later stage of ovarian cycle. Moreover, the oviposition rate (OR) was downregulated, and oocyte development was delayed after MnRPL24 knockdown. After eyestalk ablation, the MnRPL24 expression level was considerably elevated in the initial stages and decreased in the late stage of the ovarian development cycle. This investigation illustrates a possible regulatory role of MnRPL24 in the ovarian development of M. nipponense, and MnRPL24 may act as a stimulator of early ovarian development.

Deregulation of ribosomal proteins in human cancers.

The ribosome, the site for protein synthesis, is composed of ribosomal RNAs (rRNAs) and ribosomal proteins (RPs). The latter have been shown to have many ribosomal and extraribosomal functions. RPs are implicated in a variety of pathological processes, especially tumorigenesis and cell transformation. In this review, we will focus on the recent advances that shed light on the effects of RPs deregulation in different types of cancer and their roles in regulating the tumor cell fate.

The dedicated chaperones of eL43, Puf6 and Loc1 can also bind RPL43 mRNA and regulate the production of this ribosomal protein.

The level of ribosome biogenesis is highly associated with cell growth rate. Because many ribosomal proteins have extraribosomal functions, overexpression or insufficient supply of these proteins may impair cellular growth. Therefore, the supply of ribosomal proteins is tightly controlled in response to rRNA syntheses and environmental stimuli. In our previous study, two RNA-binding proteins, Puf6 and Loc1, were identified as dedicated chaperones of the ribosomal protein eL43, with which they associate to maintain its protein level and proper loading. In this study, we demonstrate that Puf6 and Loc1 interact with RPL43 mRNA. Notably, Puf6 and Loc1 usually function as a dimeric complex to bind other mRNAs; however, in this instance, the individual proteins, but not the complex form, can bind RPL43 mRNA. Thus, Puf6 or Loc1 could bind RPL43 mRNA in loc1Δ or puf6Δ, respectively. The binding of Puf6 or Loc1 caused negative effects for eL43 production: decreased RNA stability and translation of RPL43A/B mRNA. The present results suggest that these dedicated chaperones control the protein levels of eL43 from the standpoint of stability and through regulating its production.

Production, characterization, and epitope mapping of monoclonal antibodies of ribosomal protein S3 (rpS3)

ABSTRACT Ribosomal protein S3 (rpS3), a member of 40S small ribosomal subunit, is a multifunctional protein with various extra-ribosomal functions including DNA repair endonuclease activity and is secreted from cancer cells. Therefore, antibodies with high specificity against rpS3 protein could be useful cancer biomarkers. In this study, polyclonal antibody (pAb) and monoclonal antibodies (mAbs) were raised against rpS3 protein and epitope mapping was performed for each antibody; the amino acid residues of rpS3 were scanned from amino acid 185 to 243 through peptide scanning to reveal the epitopes of each mAb. Results showed that pAb R2 has an epitope from amino acid 203 to 230, mAb M7 has an epitope from amino acid 213 to 221, and mAb M8 has an epitope from amino acid 197 to 219. Taken together, novel mAbs and pAb against rpS3 were raised and mapped against rpS3 with different specific epitopes.

Overexpressed MPS-1 contributes to endometrioma development through the NF-\u03baB signaling pathway

BackgroundEndometriosis is a benign gynecological disease that shares some characteristics with malignant tumors and affects approximately 10% of women of reproductive age. Endometrioma refers to endometriosis that appears in the ovary. Metallopanstimulin-1 (MPS-1) is a component of the 40S subunit of ribosomes that has extra-ribosomal functions that contribute to the development of diseases. This study aimed to explore the expression pattern and role of MPS-1 in endometrioma development.MethodsQuantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay were used to determine the expression of MPS-1 in patients with endometrioma. Following the successful knockdown of MPS-1 by siRNA, CCK-8 assays, flow cytometry, and transwell assays were performed to detect ectopic endometrial stromal cells (EcESCs) proliferation, the rate of apoptosis, and cell cycle, migration, and invasion, respectively. Western blotting was used to explore the effect of MPS-1 knockdown on protein levels in the NF-κB signaling pathway.ResultsThe expression of MPS-1 was significantly higher in endometrioma and the serum of endometrioma patients than in the patients without endometriosis. In addition, the downregulation of MPS-1 expression inhibited EcESCs proliferation, migration, and invasion. This downregulation led to the arrest of the EcESCs cycle in the G0/G1 phase and apoptosis and depressed the NF-κB signaling pathway.ConclusionMPS-1 can regulate EcESCs proliferation, motility, invasion, apoptosis, and cell cycle via the NF-κB signaling pathway in endometrioma. This may contribute to the formation or development of endometriotic foci. This study suggests the potential role of MPS-1 in the pathogenesis of endometriosis and enabled further research into the use of MPS-1 in the clinical diagnosis of endometrioma.

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins.

Cytosolic ribosomes (cytoribosomes) are macromolecular ribonucleoprotein complexes that are assembled from ribosomal RNA and ribosomal proteins, which are essential for protein biosynthesis. Mitochondrial ribosomes (mitoribosomes) perform translation of the proteins essential for the oxidative phosphorylation system. The biogenesis of cytoribosomes and mitoribosomes includes ribosomal RNA processing, modification and binding to ribosomal proteins and is assisted by numerous biogenesis factors. This is a major energy-consuming process in the cell and, therefore, is highly coordinated and sensitive to several cellular stressors. In mitochondria, the regulation of mitoribosome biogenesis is essential for cellular respiration, a process linked to cell growth and proliferation. This review briefly overviews the key stages of cytosolic and mitochondrial ribosome biogenesis; summarizes the main steps of ribosome biogenesis alterations occurring during tumorigenesis, highlighting the changes in the expression level of cytosolic ribosomal proteins (CRPs) and mitochondrial ribosomal proteins (MRPs) in different types of tumors; focuses on the currently available information regarding the extra-ribosomal functions of CRPs and MRPs correlated to cancer; and discusses the role of CRPs and MRPs as biomarkers and/or molecular targets in cancer treatment.

Ribosomal Protein L13 Participates in Innate Immune Response Induced by Foot-and-Mouth Disease Virus.

In addition to ribosomal protein synthesis and protein translation, ribosomal proteins also participate in tumorigenesis and tumor progression, immune responses, and viral replication. Here, we show that ribosomal protein L13 (RPL13) participates in the antiviral immune response induced by foot-and-mouth disease virus (FMDV), inhibiting FMDV replication. The overexpression of RPL13 promoted the induction and activation of the promoters of the nuclear factor-κB (NF-κB) and interferon-β (IFN-β) genes, and the expression and protein secretion of the antiviral factor IFN-β and proinflammatory cytokine interleukin-6 (IL-6). The knockdown of RPL13 had the opposite effects. We also found that the FMDV 3Cpro protease interacts with RPL13, and that its activity reduces the expression of RPL13, thus antagonizing the RPL13-mediated antiviral activity. This study extends our knowledge of the extraribosomal functions of ribosomal proteins and provides new scientific information on cellular antiviral defenses and virus-antagonizing mechanisms.