Similar Datasets
Project description:We aimed to study the contribution of RNA binding proteins in shaping the highly divergent cancer spliceome
2021-09-15 | GSE87410 | GEO
Project description:RNA binding proteins in cancer spliceome
| PRJNA348692 | ENA
Project description:To investigate the contribution of RNA-binding proteins to the regulation of RNA decay we used an in vivo labelling system (Cleary et al. 2005 Nat Biotechnol. 23, 232-7) to estimate the decay rates of RBP mutants and wild type S. pombe cells
2014-11-06 | E-MTAB-2712 | biostudies-arrayexpress
Project description:Defects in the functions of RNA binding proteins (RBPs) are at the origin of many diseases; however, targeting RBPs with conventional drugs has proven difficult. PROTACs are a new class of drugs that mediate selective degradation of a target protein through a cell's ubiquitination machinery. PROTACs comprise a moiety that binds the selected protein, conjugated to a ligand of an E3 ligase. Herein, we introduce RNA-PROTACs as a new concept in the targeting of RBPs. These chimeric structures employ small RNA mimics as targeting groups that dock the RNA-binding site of the RBP, whereupon a conjugated E3-recruiting peptide derived from the HIF-1α protein directs the RBP for proteasomal degradation. We performed a proof-of-concept demonstration with the degradation of two RBPs-a stem cell factor LIN28 and a splicing factor RBFOX1-and showed their use in cancer cell lines. The RNA-PROTAC approach opens the way to rapid, selective targeting of RBPs in a rational and general fashion.
| S-EPMC7898822 | biostudies-literature
Project description:The post-transcriptional regulation of gene expression plays an important role in heart development and disease. Cardiac-specific alternative splicing, mediated by RNA-binding proteins, orchestrates the isoform switching of proteins that are essential for cardiomyocyte organization and contraction. Dysfunctions of RNA-binding proteins impair heart development and cause the main types of cardiomyopathies, which represent a heterogenous group of abnormalities that severely affect heart structure and function. In particular, mutations of RBM20 and RBFOX2 are associated with dilated cardiomyopathy, hypertrophic cardiomyopathy, or hypoplastic left heart syndrome. Functional analyses in different animal models also suggest possible roles for other RNA-binding proteins in cardiomyopathies because of their involvement in organizing cardiac gene programming. Recent studies have provided significant insights into the causal relationship between RNA-binding proteins and cardiovascular diseases. They also show the potential of correcting pathogenic mutations in RNA-binding proteins to rescue cardiomyopathy or promote cardiac regeneration. Therefore, RNA-binding proteins have emerged as promising targets for therapeutic interventions for cardiovascular dysfunction. The challenge remains to decipher how they coordinately regulate the temporal and spatial expression of target genes to ensure heart function and homeostasis. This review discusses recent advances in understanding the implications of several well-characterized RNA-binding proteins in cardiomyopathies, with the aim of identifying research gaps to promote further investigation in this field.
| S-EPMC10971380 | biostudies-literature
Project description:Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.
| S-EPMC8269357 | biostudies-literature
Project description:Identifying binding targets of RNA-binding proteins (RBPs) can greatly facilitate our understanding of their functional mechanisms. Most computational methods employ machine learning to train classifiers on either RBP-specific targets or pooled RBP-RNA interactions. The former strategy is more powerful, but it only applies to a few RBPs with a large number of known targets; conversely, the latter strategy sacrifices prediction accuracy for a wider application, since specific interaction features are inevitably obscured through pooling heterogeneous datasets. Here, we present beRBP, a dual approach to predict human RBP-RNA interaction given PWM of a RBP and one RNA sequence. Based on Random Forests, beRBP not only builds a specific model for each RBP with a decent number of known targets, but also develops a general model for RBPs with limited or null known targets. The specific and general models both compared well with existing methods on three benchmark datasets. Notably, the general model achieved a better performance than existing methods on most novel RBPs. Overall, as a composite solution overarching the RBP-specific and RBP-General strategies, beRBP is a promising tool for human RBP binding estimation with good prediction accuracy and a broad application scope.
| S-EPMC6411931 | biostudies-literature
Project description:Arrays of >5,000 Saccharomyces cerevisiae proteins were screened to identify proteins that can preferentially bind a small RNA hairpin that contains a clamped adenine motif (CAM). A CAM is required for the replication of Brome Mosaic Virus (BMV), a plant-infecting RNA virus that can replicate in S. cerevisiae. Several hits were selected for further characterization in Nicotiana benthamiana. Pseudouridine Synthase 4 (Pus4) and the Actin Patch Protein 1 (App1) modestly reduced BMV genomic plus-strand RNA accumulation, but dramatically inhibited BMV systemic spread in plants. Pus4 also prevented the encapsidation of a BMV RNA in plants and the reassembly of BMV virions in vitro. These results demonstrate the feasibility of using proteome arrays to identify specific RNA-binding proteins for antiviral activities. Furthermore, the effects of Pus4 suggest that the CAM-containing RNA motif provides a regulatory link between RNA replication and encapsidation.
| S-EPMC1805585 | biostudies-literature
Project description:To study the contribution of RNA-binding proteins (RBPs) to the regulation of RNA turnover, we used DNA microarrays to examine the transcriptome of S. pombe strains containing deletions in non-essential genes encoding RBPs
2014-11-06 | E-MTAB-2314 | biostudies-arrayexpress
Project description:Acute leukemias are genetic diseases caused by translocations or mutations, which dysregulate hematopoiesis towards malignant transformation. However, the molecular mode of action is highly versatile and ranges from direct transcriptional to post-transcriptional control, which includes RNA-binding proteins (RBPs) as crucial regulators of cell fate. RBPs coordinate RNA dynamics, including subcellular localization, translational efficiency and metabolism, by binding to their target messenger RNAs (mRNAs), thereby controlling the expression of the encoded proteins. In view of the growing interest in these regulators, this review summarizes recent research regarding the most influential RBPs relevant in acute leukemias in particular. The reported RBPs, either dysregulated or as components of fusion proteins, are described with respect to their functional domains, the pathways they affect, and clinical aspects associated with their dysregulation or altered functions.
| S-EPMC7279408 | biostudies-literature