Abstract PD15-07: Myc regulates alternative splicing through a network of RNA binding proteins in breast cancer

2021 ◽  
Author(s):  
Laura Urbanski ◽  
Brittany Angarola ◽  
Mattia Brugiolo ◽  
Marina Yurieva ◽  
Sunghee Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

scholarly journals CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lizhen Chen ◽  
Zhijie Liu ◽  
Bing Zhou ◽  
Chaoliang Wei ◽  
Yu Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Alternative Splicing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Axon Regeneration ◽  
Rna Binding Proteins ◽  
Mrna Isoforms ◽  
C Elegans ◽  
Mrna Targets

Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE Syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. Further, mRNAs for several Syntaxins show CELF2 dependent regulation. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension.

scholarly journals Alternative splicing regulation of doublesex gene by RNA-binding proteins in the silkworm Bombyx mori

RNA Biology ◽  
2019 ◽  
Vol 16 (6) ◽  
pp. 809-820 ◽  
Author(s):  
Zeng-Zhang Zheng ◽  
Xia Sun ◽  
Bei Zhang ◽  
Jia Pu ◽  
Ze-Yu Jiang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Bombyx Mori ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Splicing Regulation ◽  
Silkworm Bombyx Mori

scholarly journals Evolution of the Small Family of Alternative Splicing Modulators Nuclear Speckle RNA-Binding Proteins in Plants

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 207 ◽  
Author(s):  
Leandro Lucero ◽  
Jeremie Bazin ◽  
Johan Rodriguez Melo ◽  
Fernando Ibañez ◽  
Martín D. Crespi ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Medicago Truncatula ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nodule Development ◽  
Nuclear Speckle ◽  
Symbiotic Nodule

RNA-Binding Protein 1 (RBP1) was first identified as a protein partner of the long noncoding RNA (lncRNA) ENOD40 in Medicago truncatula, involved in symbiotic nodule development. RBP1 is localized in nuclear speckles and can be relocalized to the cytoplasm by the interaction with ENOD40. The two closest homologs to RBP1 in Arabidopsis thaliana were called Nuclear Speckle RNA-binding proteins (NSRs) and characterized as alternative splicing modulators of specific mRNAs. They can recognize in vivo the lncRNA ALTERNATIVE SPLICING COMPETITOR (ASCO) among other lncRNAs, regulating lateral root formation. Here, we performed a phylogenetic analysis of NSR/RBP proteins tracking the roots of the family to the Embryophytes. Strikingly, eudicots faced a reductive trend of NSR/RBP proteins in comparison with other groups of flowering plants. In Medicago truncatula and Lotus japonicus, their expression profile during nodulation and in specific regions of the symbiotic nodule was compared to that of the lncRNA ENOD40, as well as to changes in alternative splicing. This hinted at distinct and specific roles of each member during nodulation, likely modulating the population of alternatively spliced transcripts. Our results establish the basis to guide future exploration of NSR/RBP function in alternative splicing regulation in different developmental contexts along the plant lineage.

scholarly journals The CELF Family of RNA Binding Proteins Is Implicated in Cell-Specific and Developmentally Regulated Alternative Splicing

2001 ◽  
Vol 21 (4) ◽  
pp. 1285-1296 ◽  
Author(s):  
Andrea N. Ladd ◽  
Nicolas Charlet-B. ◽  
Thomas A. Cooper
Keyword(s):  
Alternative Splicing ◽  
Heart Development ◽  
Binding Proteins ◽  
Rna Binding ◽  
Striated Muscle ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
Exon Inclusion

ABSTRACT Alternative splicing of cardiac troponin T (cTNT) exon 5 undergoes a developmentally regulated switch such that exon inclusion predominates in embryonic, but not adult, striated muscle. We previously described four muscle-specific splicing enhancers (MSEs) within introns flanking exon 5 in chicken cTNT that are both necessary and sufficient for exon inclusion in embryonic muscle. We also demonstrated that CUG-binding protein (CUG-BP) binds a conserved CUG motif within a human cTNT MSE and positively regulates MSE-dependent exon inclusion. Here we report that CUG-BP is one of a novel family of developmentally regulated RNA binding proteins that includes embryonically lethal abnormal vision-type RNA binding protein 3 (ETR-3). This family, which we call CELF proteins for CUG-BP- and ETR-3-like factors, specifically bound MSE-containing RNAs in vitro and activated MSE-dependent exon inclusion of cTNT minigenes in vivo. The expression of two CELF proteins is highly restricted to brain. CUG-BP, ETR-3, and CELF4 are more broadly expressed, and expression is developmentally regulated in striated muscle and brain. Changes in the level of expression and isoforms of ETR-3 in two different developmental systems correlated with regulated changes in cTNT splicing. A switch from cTNT exon skipping to inclusion tightly correlated with induction of ETR-3 protein expression during differentiation of C2C12 myoblasts. During heart development, the switch in cTNT splicing correlated with a transition in ETR-3 protein isoforms. We propose that ETR-3 is a major regulator of cTNT alternative splicing and that the CELF family plays an important regulatory role in cell-specific alternative splicing during normal development and disease.

scholarly journals Prediction of breast cancer proteins using molecular descriptors and artificial neural networks: a focus on cancer immunotherapy proteins, metastasis driver proteins, and RNA-binding proteins

2019 ◽  
Author(s):  
Andrés López-Cortés ◽  
Alejandro Cabrera-Andrade ◽  
José M. Vázquez-Naya ◽  
Alejandro Pazos ◽  
Humberto Gonzáles-Díaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neural Networks ◽  
Cancer Immunotherapy ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Operating Characteristics ◽  
Associated Proteins ◽  
Artificial Neural ◽  
New Biomarkers

ABSTRACTBackgroundBreast cancer (BC) is a heterogeneous disease characterized by an intricate interplay between different biological aspects such as ethnicity, genomic alterations, gene expression deregulation, hormone disruption, signaling pathway alterations and environmental determinants. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design.MethodsThis work is proposing accurate prediction classifier for BC proteins using six sets of protein sequence descriptors and 13 machine learning methods. After using a univariate feature selection for the mix of five descriptor families, the best classifier was obtained using multilayer perceptron method (artificial neural network) and 300 features.ResultsThe performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980 ± 0.0037 and accuracy of 0.936 ± 0.0056 (3-fold cross-validation). Regarding the prediction of 4504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1.ConclusionsThis powerful model predicts several BC-related proteins which should be deeply studied to find new biomarkers and better therapeutic targets. The script and the results are available as a free repository at https://github.com/muntisa/neural-networks-for-breast-cancer-proteins.

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