scholarly journals CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs

Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 49 ◽  
Author(s):  
Jiao Luo ◽  
Bo Jiang ◽  
Chao Li ◽  
Xiaoling Jia ◽  
Dayong Shi
Keyword(s):  
Signaling Pathways ◽  
Insulin Signaling ◽  
Rna Splicing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Red Alga ◽  
Total Serum ◽  
Global Changes ◽  
Synthetic Derivative ◽  
Rhodomela Confervoides

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found that CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27 effectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC) and triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased insulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to systemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was performed to investigate global changes in phosphorylation. Enriched GO annotation showed that most regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG analysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27 treatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of mRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our results suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the insulin signaling pathways and modulating RNA splicing-associated RBPs.

scholarly journals Novel Insights into YB-1 Signaling and Cell Death Decisions

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3306
Author(s):  
Aneri Shah ◽  
Jonathan A. Lindquist ◽  
Lars Rosendahl ◽  
Ingo Schmitz ◽  
Peter R. Mertens
Keyword(s):  
Stress Responses ◽  
Rna Splicing ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Inflammatory Responses ◽  
Rna Binding Proteins ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Tumor Therapy ◽  
Inflammatory Microenvironment

YB-1 belongs to the evolutionarily conserved cold-shock domain protein family of RNA binding proteins. YB-1 is a well-known transcriptional and translational regulator, involved in cell cycle progression, DNA damage repair, RNA splicing, and stress responses. Cell stress occurs in many forms, e.g., radiation, hyperthermia, lipopolysaccharide (LPS) produced by bacteria, and interferons released in response to viral infection. Binding of the latter factors to their receptors induces kinase activation, which results in the phosphorylation of YB-1. These pathways also activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a well-known transcription factor. NF-κB is upregulated following cellular stress and orchestrates inflammatory responses, cell proliferation, and differentiation. Inflammation and cancer are known to share common mechanisms, such as the recruitment of infiltrating macrophages and development of an inflammatory microenvironment. Several recent papers elaborate the role of YB-1 in activating NF-κB and signaling cell survival. Depleting YB-1 may tip the balance from survival to enhanced apoptosis. Therefore, strategies that target YB-1 might be a viable therapeutic option to treat inflammatory diseases and improve tumor therapy.

scholarly journals Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function

2020 ◽  
Author(s):  
Fiona Haward ◽  
Magdalena M. Maslon ◽  
Patricia L. Yeyati ◽  
Nicolas Bellora ◽  
Jan N. Hansen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Rna Splicing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Small Body ◽  
Splicing Factor ◽  
Nuclear Retention ◽  
Ciliary Ultrastructure ◽  
Retention Signal

AbstractShuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. The SR family proteins regulate RNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus. Srsf1NRS/NRS mutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility in cells derived from this mouse model. These results demonstrate that SRSF1 shuttling is used to reprogram gene expression networks in the context of high cellular demands, as observed here, during motile ciliogenesis.

scholarly journals Cellular RNA Binding Proteins NS1-BP and hnRNP K Regulate Influenza A Virus RNA Splicing

2013 ◽  
Vol 9 (6) ◽  
pp. e1003460 ◽  
Author(s):  
Pei-Ling Tsai ◽  
Ni-Ting Chiou ◽  
Sharon Kuss ◽  
Adolfo García-Sastre ◽  
Kristen W. Lynch ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Rna Splicing ◽  
Influenza A ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Hnrnp K ◽  
Virus Rna

scholarly journals Defective control of pre–messenger RNA splicing in human disease

2016 ◽  
Vol 212 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Benoit Chabot ◽  
Lulzim Shkreta
Keyword(s):  
Alternative Splicing ◽  
Human Disease ◽  
Rna Splicing ◽  
Messenger Rna ◽  
Recent Progress ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Proteins ◽  
Regulatory Sequence ◽  
Sequence Elements

Examples of associations between human disease and defects in pre–messenger RNA splicing/alternative splicing are accumulating. Although many alterations are caused by mutations in splicing signals or regulatory sequence elements, recent studies have noted the disruptive impact of mutated generic spliceosome components and splicing regulatory proteins. This review highlights recent progress in our understanding of how the altered splicing function of RNA-binding proteins contributes to myelodysplastic syndromes, cancer, and neuropathologies.

scholarly journals Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

2018 ◽  
Author(s):  
Konstantin Krismer ◽  
Shohreh Varmeh ◽  
Molly A. Bird ◽  
Anna Gattinger ◽  
Yi Wen Kong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Stability ◽  
Protein Translation ◽  
State Transitions ◽  
Global Changes ◽  
Expression Data ◽  
Platinum Based Chemotherapy

AbstractRNA-binding proteins (RBPs) play critical roles in regulating gene expression by modulating splicing, RNA stability, and protein translation. In response to various stimuli, alterations in RBP function contribute to global changes in gene expression, but identifying which specific RBPs are responsible for the observed changes in gene expression patterns remains an unmet need. Here, we presentTransitea multi-pronged computational approach that systematically infers RBPs influencing gene expression changes through alterations in RNA stability and degradation. As a proof of principle, we applied Transite to public RNA expression data from human patients with non-small cell lung cancer whose tumors were sampled at diagnosis, or after recurrence following treatment with platinum-based chemotherapy. Transite implicated known RBP regulators of the DNA damage response and identified hnRNPC as a new modulator of chemotherapeutic resistance, which we subsequently validated experimentally. Transite serves as a generalizable framework for the identification of RBPs responsible for gene expression changes that drive cell-state transitions and adds additional value to the vast wealth of publicly-available gene expression data.

scholarly journals miRNA-Based Regulation of Alternative RNA Splicing in Metazoans

2021 ◽  
Vol 22 (21) ◽  
pp. 11618
Author(s):  
Anna L. Schorr ◽  
Marco Mangone
Keyword(s):  
Neurological Disorders ◽  
Rna Splicing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Non Coding Rnas ◽  
Specific Mrna

Alternative RNA splicing is an important regulatory process used by genes to increase their diversity. This process is mainly executed by specific classes of RNA binding proteins that act in a dosage-dependent manner to include or exclude selected exons in the final transcripts. While these processes are tightly regulated in cells and tissues, little is known on how the dosage of these factors is achieved and maintained. Several recent studies have suggested that alternative RNA splicing may be in part modulated by microRNAs (miRNAs), which are short, non-coding RNAs (~22 nt in length) that inhibit translation of specific mRNA transcripts. As evidenced in tissues and in diseases, such as cancer and neurological disorders, the dysregulation of miRNA pathways disrupts downstream alternative RNA splicing events by altering the dosage of splicing factors involved in RNA splicing. This attractive model suggests that miRNAs can not only influence the dosage of gene expression at the post-transcriptional level but also indirectly interfere in pre-mRNA splicing at the co-transcriptional level. The purpose of this review is to compile and analyze recent studies on miRNAs modulating alternative RNA splicing factors, and how these events contribute to transcript rearrangements in tissue development and disease.

scholarly journals Binding patterns of RNA-binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Masahiro Onoguchi ◽  
Chao Zeng ◽  
Ayako Matsumaru ◽  
Michiaki Hamada
Keyword(s):  
Rna Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Rna Sequences ◽  
Rna Elements ◽  
Long Interspersed Element ◽  
Functional Rna

Abstract Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.

scholarly journals RNA-Binding Proteins as Targets to Improve Salt Stress Tolerance in Crops

Agronomy ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 250 ◽  
Author(s):  
Sara Rosa Téllez ◽  
Rodoldphe Kanhonou ◽  
Carlos Castellote Bellés ◽  
Ramón Serrano ◽  
Paula Alepuz ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Sugar Beet ◽  
Rna Splicing ◽  
Yeast Strain ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Crop Improvement ◽  
Salt Toxicity

Salt stress drastically reduce crop productivity. In order to identify genes that could improve crop salt tolerance, we randomly expressed a cDNA library of the halotolerant sugar beet in a sodium-sensitive yeast strain. We identified six sugar beet genes coding for RNA binding proteins (RBP) able to increase the yeast Na+-tolerance. Two of these genes, named Beta vulgaris Salt Tolerant 3 (BvSATO3) and BvU2AF35b, participate in RNA splicing. The other four BvSATO genes (BvSATO1, BvSATO2, BvSATO4 and BvSATO6) are putatively involved in other processes of RNA metabolism. BvU2AF35b improved the growth of a wild type yeast strain under salt stress, and also in mutant backgrounds with impaired splicing, thus confirming that splicing is a target of salt toxicity. To validate the yeast approach, we characterized BvSATO1 in sugar beet and Arabidopsis. BvSATO1 expression was repressed by salt treatment in sugar beet, suggesting that this gene could be a target of salt toxicity. Expression of BvSATO1 in Arabidopsis increased the plant salt tolerance. Our results suggest that not only RNA splicing, but RNA metabolic processes such as such as RNA stability or nonsense-mediated mRNA decay may also be affected by salt stress and could be biotechnological targets for crop improvement.

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