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Bioscience Reports Jan 2021Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis,...
Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets (GSE65194 and GSE76124). Then Gene ontology (GO) and KEGG analysis were performed by DAVID database, protein-protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC.
Topics: Computational Biology; Female; Gene Ontology; Humans; Middle Aged; Protein Interaction Maps; Real-Time Polymerase Chain Reaction; Ribosomal Proteins; Triple Negative Breast Neoplasms
PubMed: 33305312
DOI: 10.1042/BSR20200869 -
Critical Reviews in Immunology 2015Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence... (Review)
Review
Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence is emerging that suggests ribosomal proteins are also capable of performing tissue-restricted, regulatory functions that impact normal development and pathological conditions, including cancer. The challenge in studying such regulatory functions is that elimination of many ribosomal proteins also disrupts ribosome biogenesis and/or function. Thus, it is difficult to determine whether developmental abnormalities resulting from ablation of a ribosomal protein result from loss of core ribosome functions or from loss of the regulatory function of the ribosomal protein. Rpl22, a ribosomal protein component of the large 60S subunit, provides insight into this conundrum; Rpl22 is dispensable for both ribosome biogenesis and protein synthesis yet its ablation causes tissue-restricted disruptions in development. Here we review evidence supporting the regulatory functions of Rpl22 and other ribosomal proteins.
Topics: Animals; Dogs; Embryonic Development; Hematopoiesis; Humans; Organ Specificity; RNA-Binding Proteins; Ribosomal Proteins; Ribosomes
PubMed: 26853850
DOI: 10.1615/critrevimmunol.v35.i5.30 -
The Journal of Cell Biology Mar 1985Using antibodies to various nucleolar and ribosomal proteins, we define, by immunolocalization in situ, the distribution of nucleolar proteins in the different... (Comparative Study)
Comparative Study Review
Using antibodies to various nucleolar and ribosomal proteins, we define, by immunolocalization in situ, the distribution of nucleolar proteins in the different morphological nucleolar subcompartments. In the present study we describe the nucleolar localization of a specific ribosomal protein (S1) by immunofluorescence and immunoelectron microscopy using a monoclonal antibody (RS1-105). In immunoblotting experiments, this antibody reacts specifically with the largest and most acidic protein of the small ribosomal subunit (S1) and shows wide interspecies cross-reactivity from amphibia to man. Beside its localization in cytoplasmic ribosomes, this protein is found to be specifically localized in the granular component of the nucleolus and in distinct granular aggregates scattered over the nucleoplasm. This indicates that ribosomal protein S1, in contrast to reports on other ribosomal proteins, is not bound to nascent pre-rRNA transcripts but attaches to preribosomes at later stages of rRNA processing and maturation. This protein is not detected in the residual nucleolar structures of cells inactive in rRNA synthesis such as amphibian and avian erythrocytes. During mitosis, the nucleolar material containing ribosomal protein S1 undergoes a remarkable transition and shows a distribution distinct from that of several other nucleolar proteins. In prophase, the nucleolus disintegrates and protein S1 appears in numerous small granules scattered throughout the prophase nucleus. During metaphase and anaphase, a considerable amount of this protein is found in association with the surfaces of all chromosomes and finely dispersed in the cell plasm. In telophase, protein S1-containing material reaccumulates in granular particles in the nucleoplasm of the newly formed nuclei and, finally, in the re-forming nucleoli. These observations indicate that the nucleolus-derived particles containing ribosomal protein S1 are different from cytoplasmic ribosomes and, in the living cell, are selectively recollected after mitosis into the newly formed nuclei and translocated into a specific nucleolar subcompartment, i.e., the granular component. The nucleolar location of ribosomal protein S1 and its rearrangement during mitosis is discussed in relation to the distribution of other nucleolar proteins.
Topics: Animals; Antibodies, Monoclonal; Cell Nucleolus; Cross Reactions; Humans; Immunochemistry; Interphase; Mice; Mitosis; RNA, Ribosomal; Rats; Ribosomal Proteins; Species Specificity
PubMed: 3882724
DOI: 10.1083/jcb.100.3.873 -
Molecular Biology and Evolution Jan 2021The ribosome is an essential cellular machine performing protein biosynthesis. Its structure and composition are highly conserved in all species. However, some bacteria...
The ribosome is an essential cellular machine performing protein biosynthesis. Its structure and composition are highly conserved in all species. However, some bacteria have been reported to have an incomplete set of ribosomal proteins. We have analyzed ribosomal protein composition in 214 small bacterial genomes (<1 Mb) and found that although the ribosome composition is fairly stable, some ribosomal proteins may be absent, especially in bacteria with dramatically reduced genomes. The protein composition of the large subunit is less conserved than that of the small subunit. We have identified the set of frequently lost ribosomal proteins and demonstrated that they tend to be positioned on the ribosome surface and have fewer contacts to other ribosome components. Moreover, some proteins are lost in an evolutionary correlated manner. The reduction of ribosomal RNA is also common, with deletions mostly occurring in free loops. Finally, the loss of the anti-Shine-Dalgarno sequence is associated with the loss of a higher number of ribosomal proteins.
Topics: Genome Size; Genome, Bacterial; Ribosomal Proteins; Ribosomes
PubMed: 32681797
DOI: 10.1093/molbev/msaa184 -
RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits.Molecular Cell Apr 2023RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important...
RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chromatography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS)," we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 3' end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to increase the efficiency of 3' end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disassociated subunits in mammalian cells.
Topics: Animals; RNA Polymerase II; Transcription, Genetic; Ribosomal Proteins; Ribosomes; Protein Subunits; Mammals
PubMed: 36924766
DOI: 10.1016/j.molcel.2023.02.028 -
Scientific Reports Nov 2021Four-stranded G-quadruplex (G4) structures form from guanine-rich tracts, but the extent of their formation in cellular RNA and details of their role in RNA biology...
Four-stranded G-quadruplex (G4) structures form from guanine-rich tracts, but the extent of their formation in cellular RNA and details of their role in RNA biology remain poorly defined. Herein, we first delineate the presence of endogenous RNA G4s in the human cytoplasmic transcriptome via the binding sites of G4-interacting proteins, DDX3X (previously published), DHX36 and GRSF1. We demonstrate that a sub-population of these RNA G4s are reliably detected as folded structures in cross-linked cellular lysates using the G4 structure-specific antibody BG4. The 5' UTRs of protein coding mRNAs show significant enrichment in folded RNA G4s, particularly those for ribosomal proteins. Mutational disruption of G4s in ribosomal protein UTRs alleviates translation in vitro, whereas in cells, depletion of G4-resolving helicases or treatment with G4-stabilising small molecules inhibit the translation of ribosomal protein mRNAs. Our findings point to a common mode for translational co-regulation mediated by G4 structures. The results reveal a potential avenue for therapeutic intervention in diseases with dysregulated translation, such as cancer.
Topics: 5' Untranslated Regions; Binding Sites; G-Quadruplexes; Humans; Nucleic Acid Conformation; Protein Binding; RNA, Messenger; Ribosomal Proteins
PubMed: 34815422
DOI: 10.1038/s41598-021-01847-6 -
Scientific Reports Jan 2018Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated...
Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation. Contrary to optimal culture conditions, heat stressed S223A mutant cells exhibited increased heat resistance and induced heat shock proteins. Taken together, an intracellular signal transduction pathway involving Ypk1/Pkc1 seemed to play an important role in ribosome biogenesis and subsequent cellular translation, utilizing uS7 as a substrate.
Topics: Heat-Shock Response; Mutation; Phosphorylation; Protein Domains; Protein Kinase C; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Ribosomal Proteins; Ribosome Subunits, Small; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 29352143
DOI: 10.1038/s41598-018-19652-z -
Nucleic Acids Research Jan 1999Structures of a number of ribosomal proteins have now been determined by crystallography and NMR, though the complete structure of a ribosomal protein-rRNA complex has... (Review)
Review
Structures of a number of ribosomal proteins have now been determined by crystallography and NMR, though the complete structure of a ribosomal protein-rRNA complex has yet to be solved. However, some ribosomal protein structures show strong similarity to well-known families of DNA or RNA binding proteins for which structures in complex with cognate nucleic acids are available. Comparison of the known nucleic acid binding mechanisms of these non-ribosomal proteins with the most highly conserved surfaces of similar ribosomal proteins suggests ways in which the ribosomal proteins may be binding RNA. Three binding motifs, found in four ribosomal proteins so far, are considered here: homeodomain-like alpha-helical proteins (L11), OB fold proteins (S1 and S17) and RNP consensus proteins (S6). These comparisons suggest that ribosomal proteins combine a small number of fundamental strategies to develop highly specific RNA recognition sites.
Topics: Amino Acid Sequence; Binding Sites; Conserved Sequence; Homeodomain Proteins; Molecular Sequence Data; Protein Binding; Protein Structure, Secondary; RNA, Ribosomal; Ribonucleoproteins; Ribosomal Proteins; Sequence Homology, Amino Acid
PubMed: 9862955
DOI: 10.1093/nar/27.2.381 -
BioMed Research International 2017The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date,...
The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date, three ribosomal protein genes, , , and , have been found to be differentially expressed in cell lines derived from NPC tumors. This raises the possibility of more ribosomal protein genes that could be associated with NPC. In this study, we investigated the expression profiles of eight ribosomal protein genes, , and , in six NPC-derived cell lines (HONE-1, SUNE1, HK1, TW01, TW04, and C666-1). Their expression levels were compared with that of a nonmalignant nasopharyngeal epithelial cell line (NP69) using quantitative real-time PCR (RT-qPCR) assay. Of the eight genes studied, the expressions of four ribosomal protein genes and were found to be significantly downregulated in NPC cell lines relative to NP69. Our findings provide novel empirical evidence of these four ribosomal protein genes as NPC-associated genetic factors and reinforce the relevance of ribosomal proteins in the carcinogenesis of nasopharyngeal cancer.
Topics: Carcinoma; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Ribosomal Proteins
PubMed: 28791303
DOI: 10.1155/2017/4876954 -
Archives of Microbiology Apr 2021As intracellular parasites, viruses depend heavily on host cell structures and their functions to complete their life cycle and produce new viral particles. Viruses... (Review)
Review
As intracellular parasites, viruses depend heavily on host cell structures and their functions to complete their life cycle and produce new viral particles. Viruses utilize or modulate cellular translational machinery to achieve efficient replication; the role of ribosome biogenesis and protein synthesis in viral replication particularly highlights the importance of the ribosome quantity and/or quality in controlling viral protein synthesis. Recently reported studies have demonstrated that ribosome biogenesis factors (RBFs) and ribosomal proteins (RPs) act as multifaceted regulators in selective translation of viral transcripts. Here we summarize the recent literature on RBFs and RPs and their association with subcellular redistribution, post-translational modification, enzyme catalysis, and direct interaction with viral proteins. The advances described in this literature establish a rationale for targeting ribosome production and function in the design of the next generation of antiviral agents.
Topics: Gene Expression Regulation, Viral; Protein Biosynthesis; Protein Processing, Post-Translational; Ribosomal Proteins; Ribosomes; Viral Proteins; Virus Replication; Viruses
PubMed: 33124672
DOI: 10.1007/s00203-020-02094-5