Ribonucleic Acid Binding Proteins Research Articles

637 Messenger ribonucleic acid binding proteins PTBP1 and HNRNPL modulate cystic fibrosis transmembrane conductance regulator messenger ribonucleic acid abundance

637 Messenger ribonucleic acid binding proteins PTBP1 and HNRNPL modulate cystic fibrosis transmembrane conductance regulator messenger ribonucleic acid abundance

Metabolic Reprogramming of Liver Fibrosis.

Liver fibrosis is an excessive and imbalanced deposition of fibrous extracellular matrix (ECM) that is associated with the hepatic wound-healing response. It is also the common mechanism that contributes to the impairment of the liver function that is observed in many chronic liver diseases (CLD). Despite the efforts, no effective therapy against fibrosis exists yet. Worryingly, due to the growing obesity pandemic, fibrosis incidence is on the rise. Here, we aim to summarize the main components and mechanisms involved in the progression of liver fibrosis, with special focus on the metabolic regulation of key effectors of fibrogenesis, hepatic stellate cells (HSCs), and their role in the disease progression. Hepatic cells that undergo metabolic reprogramming require a tightly controlled, fine-tuned cellular response, allowing them to meet their energetic demands without affecting cellular integrity. Here, we aim to discuss the role of ribonucleic acid (RNA)-binding proteins (RBPs), whose dynamic nature being context- and stimuli-dependent make them very suitable for the fibrotic situation. Thus, we will not only summarize the up-to-date literature on the metabolic regulation of HSCs in liver fibrosis, but also on the RBP-dependent post-transcriptional regulation of this metabolic switch that results in such important consequences for the progression of fibrosis and CLD.

A Novel RNA-Binding Protein-Based Nomogram for Predicting Survival of Patients with Gastric Cancer.

BackgroundWe attempted to develop a prognostic model and characterize molecular subtypes for gastric cancer on the basis of ribonucleic acid (RNA)-binding proteins (RBPs).Material/MethodsRNA sequence data of gastric cancer were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen survival-related RBPs, followed by least absolute shrinkage and selection operator Cox modeling. Overall and stratified survival analysis was carried out between high and low risk score groups, followed by receiver operator characteristic curve construction. Univariate and multivariate survival analysis was applied to assess its independent prognostic potential. A nomogram was constructed by combining age and the risk score, which was verified by calibration curves and decision curve analyses for 1-, 3-, and 5-year survival. Molecular subtypes were identified using nonnegative matrix factorization method. Clinical features of the identified subtypes were characterized on prognosis, drug sensitivity, and immune infiltration. An external Gene Expression Omnibus dataset was used to verify the above findings.ResultsOn the basis of 44 survival-related RBPs, a robust prognostic 15-RBP signature was constructed. Patients with high risk score had a poorer prognosis than those with low risk score. The risk score had good performance in predicting clinical outcomes for 1-, 3-, and 5-year survival. The signature was effectively independent of other clinical features. The nomogram model combining age and the 15-RBP prognostic model exhibited better practicality and reliability for prognosis. RBP expression data were utilized to define 2 distinct molecular subtypes obviously related to survival outcomes, chemotherapeutic drug sensitivity, and immune infiltration.ConclusionsOur study provides a nomogram model that consists of age and a 15-RBP signature and identifies 2 molecular subtypes for gastric cancer that possess potential value for preclinical, clinical, and translational research on gastric cancer.

Development and Validation of an RNA-Binding Protein-Based Prognostic Model for Ovarian Serous Cystadenocarcinoma.

Ribonucleic acid-binding proteins (RBPs) are reportedly involved in tumor progression and recurrence; however, the functions and mechanisms of action of RBPs in ovarian serous cystadenocarcinoma (OSC) are not known. To address these issues, gene expression profiles of OSC tissues from The Cancer Genome Atlas (TCGA) and normal tissues from the Genotype-Tissue Expression database were compared in order to identify RBPs that are differentially expressed in OSC. We also analyzed the biological functions of these RBPs and their relationship to clinical outcome. There were 190 RBPs that were differentially expressed between OSC and normal tissues, including 93 that were upregulated and 97 that were downregulated. Five of the RBPs were used to construct a prediction model that was evaluated by univariate and multivariate Cox regression analyses. TCGA data were randomly divided into training and test cohorts, and further categorized into high- and low-risk groups according to risk score in the model. The overall survival (OS) of the high-risk group was shorter than that of the low-risk group (training cohort P = 0.0007596; test cohort P = 0.002219). The area under the receiver operating characteristic curve of the training and test cohorts was 0.701 and 0.638, respectively, demonstrating that the model had good predictive power. A nomogram was established to quantitatively describe the relationship between the five prognostic RBPs and OS in OSC, which can be useful for developing individualized management strategies for patients.

Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features

In myotonic dystrophy type 1 (DM1), the CUG expansion (CUGexp) in the 3' untranslated region of the dystrophia myotonica protein kinase messenger ribonucleic acid affects the homeostasis of ribonucleic acid-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 mice and patients and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease. Interestingly, the classic DM1 mouse model human skeletal actin long repeat (HSALR) lacks overt atrophy while expressing CUGexp transcripts and elevated levels of endogenous Staufen1, suggesting a lower sensitivity to atrophic signaling in this model. We report that further overexpression of Staufen1 in the DM1 mouse model HSALR causes a myopathy via inhibition of protein kinase B signaling through an increase in phosphatase tensin homolog, leading to the expression of atrogenes. Interestingly, we also show that Staufen1 regulates the expression of muscleblind-like splicing regulator 1 and CUG-binding protein elav-like family member 1 in wild-type and DM1 skeletal muscle. Together, data obtained from these new DM1 mouse models provide evidence for the role of Staufen1 as an atrophy-associated gene that impacts progressive muscle wasting in DM1. Accordingly, our findings highlight the potential of Staufen1 as a therapeutic target and biomarker.

Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles.

BackgroundEbola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections. We have previously shown that EBOV VP40 in exosomes causes recipient immune cell death.MethodsUsing VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death. Transcription of cyclin D1 and nuclear localization of VP40 were examined via kinase and chromatin immunoprecipitation assays. Extracellular vesicle contents were characterized by mass spectrometry, cytokine array, and western blot. Biosafety level-4 facilities were used for wild-type Ebola virus infection studies.ResultsVP40 EVs induced apoptosis in recipient T cells and monocytes. VP40 clones were accelerated in growth due to cyclin D1 upregulation, and nuclear VP40 was found bound to the cyclin D1 promoter. Accelerated cell cycling was related to EV biogenesis, resulting in fewer but larger EVs. VP40 EV contents were enriched in ribonucleic acid-binding proteins and cytokines (interleukin-15, transforming growth factor-β1, and interferon-γ). Finally, EBOV-infected cell and animal EVs contained VP40, nucleoprotein, and glycoprotein.ConclusionsNuclear VP40 upregulates cyclin D1 levels, resulting in dysregulated cell cycle and EV biogenesis. Packaging of cytokines and EBOV proteins into EVs from infected cells may be responsible for the decimation of immune cells during EBOV pathogenesis.

A cDNA encoding a cold-induced glycine-rich RNA binding protein from Prunus avium expressed in embryonic axes

A cDNA clone encoding a presumed full-length glycine-rich ribonucleic acid (RNA) binding protein was isolated from a λ-ZAP Express cDNA library generated from primarily nondormant Prunus avium (wild cherry) embryonic axes. The cDNA, designated Pa-RRM-GRP1 ( Prunus avium RNA recognition motif glycine-rich protein 1), contains a single N-terminal RNA recognition motif (RRM) and single C-terminal glycine-rich domain. The glycine-rich domain is unusually long at 91 amino acids, 58 of which are glycines. The 534-base pair (bp) open reading frame (ORF) of this clone encodes a 178-amino-acid polypeptide with a predicted molecular weight of 17.33 kDa and p I of 7.84. Comparative sequence alignment of Pa-RRM-GRP1 reveals extensive homology to known and presumed glycine-rich RNA binding proteins from angiosperms and gymnosperms. Genomic Southern blot analysis suggests that this gene exists as a single copy in P. avium. Expression of this gene in P. avium embryonic axes during low-temperature dormancy-breaking treatments was studied and found to be induced by cold (3 °C) using real-time PCR of total cDNA supported by Northern blot analysis of total RNA. Expression dropped during prolonged storage at 3 °C and was reduced to control levels by interruption of cold treatment by warming to 20 °C.

Crystal structure of the ribosomal protein S6 from Thermus thermophilus.

The amino acid sequence and crystal structure of the ribosomal protein S6 from the small ribosomal subunit of Thermus thermophilus have been determined. S6 is a small protein with 101 amino acid residues. The 3D structure, which was determined to 2.0 A resolution, consists of a four-stranded anti-parallel beta-sheet with two alpha-helices packed on one side. Similar folding patterns have been observed for other ribosomal proteins and may suggest an original RNA-interacting motif. Related topologies are also found in several other nucleic acid-interacting proteins and based on the assumption that the structure of the ribosome was established early in the molecular evolution, the possibility that an ancestral RNA-interacting motif in ribosomal proteins is the evolutionary origin for the nucleic acid-interacting domain in large classes of ribonucleic acid binding proteins should be considered.

Crystal structure of the ribosomal protein S6 from Thermus thermophilus.

Research Article15 March 1994free access Crystal structure of the ribosomal protein S6 from Thermus thermophilus. M. Lindahl M. Lindahl Chemical Center, University of Lund, Sweden. Search for more papers by this author L.A. Svensson L.A. Svensson Chemical Center, University of Lund, Sweden. Search for more papers by this author A. Liljas A. Liljas Chemical Center, University of Lund, Sweden. Search for more papers by this author S.E. Sedelnikova S.E. Sedelnikova Chemical Center, University of Lund, Sweden. Search for more papers by this author I.A. Eliseikina I.A. Eliseikina Chemical Center, University of Lund, Sweden. Search for more papers by this author N.P. Fomenkova N.P. Fomenkova Chemical Center, University of Lund, Sweden. Search for more papers by this author N. Nevskaya N. Nevskaya Chemical Center, University of Lund, Sweden. Search for more papers by this author S.V. Nikonov S.V. Nikonov Chemical Center, University of Lund, Sweden. Search for more papers by this author M.B. Garber M.B. Garber Chemical Center, University of Lund, Sweden. Search for more papers by this author T.A. Muranova T.A. Muranova Chemical Center, University of Lund, Sweden. Search for more papers by this author M. Lindahl M. Lindahl Chemical Center, University of Lund, Sweden. Search for more papers by this author L.A. Svensson L.A. Svensson Chemical Center, University of Lund, Sweden. Search for more papers by this author A. Liljas A. Liljas Chemical Center, University of Lund, Sweden. Search for more papers by this author S.E. Sedelnikova S.E. Sedelnikova Chemical Center, University of Lund, Sweden. Search for more papers by this author I.A. Eliseikina I.A. Eliseikina Chemical Center, University of Lund, Sweden. Search for more papers by this author N.P. Fomenkova N.P. Fomenkova Chemical Center, University of Lund, Sweden. Search for more papers by this author N. Nevskaya N. Nevskaya Chemical Center, University of Lund, Sweden. Search for more papers by this author S.V. Nikonov S.V. Nikonov Chemical Center, University of Lund, Sweden. Search for more papers by this author M.B. Garber M.B. Garber Chemical Center, University of Lund, Sweden. Search for more papers by this author T.A. Muranova T.A. Muranova Chemical Center, University of Lund, Sweden. Search for more papers by this author Author Information M. Lindahl1, L.A. Svensson1, A. Liljas1, S.E. Sedelnikova1, I.A. Eliseikina1, N.P. Fomenkova1, N. Nevskaya1, S.V. Nikonov1, M.B. Garber1 and T.A. Muranova1 1Chemical Center, University of Lund, Sweden. The EMBO Journal (1994)13:1249-1254https://doi.org/10.1002/j.1460-2075.1994.tb06376.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The amino acid sequence and crystal structure of the ribosomal protein S6 from the small ribosomal subunit of Thermus thermophilus have been determined. S6 is a small protein with 101 amino acid residues. The 3D structure, which was determined to 2.0 A resolution, consists of a four-stranded anti-parallel beta-sheet with two alpha-helices packed on one side. Similar folding patterns have been observed for other ribosomal proteins and may suggest an original RNA-interacting motif. Related topologies are also found in several other nucleic acid-interacting proteins and based on the assumption that the structure of the ribosome was established early in the molecular evolution, the possibility that an ancestral RNA-interacting motif in ribosomal proteins is the evolutionary origin for the nucleic acid-interacting domain in large classes of ribonucleic acid binding proteins should be considered. Previous ArticleNext Article Volume 13Issue 61 March 1994In this issue RelatedDetailsLoading ...