scholarly journals RNA-Seq analysis in mutant zebrafish reveals role of U1C protein in alternative splicing regulation

2011 ◽  
Vol 30 (10) ◽  
pp. 1965-1976 ◽  
Author(s):  
Tanja Dorothe Rösel ◽  
Lee-Hsueh Hung ◽  
Jan Medenbach ◽  
Katrin Donde ◽  
Stefan Starke ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splicing Regulation ◽  
Rna Seq

scholarly journals Alternative Splicing Regulation of an Alzheimer’s Risk Variant in CLU

2020 ◽  
Vol 21 (19) ◽  
pp. 7079
Author(s):  
Seonggyun Han ◽  
Kwangsik Nho ◽  
Younghee Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alternative Splicing ◽  
Genetic Variants ◽  
Temporal Cortex ◽  
Integrative Approach ◽  
Splicing Regulation ◽  
Rna Seq ◽  
Risk Variant

Clusterin (CLU) is one of the risk genes most associated with late onset Alzheimer’s disease (AD), and several genetic variants in CLU are associated with AD risk. However, the functional role of known AD risk genetic variants in CLU has been little explored. We investigated the effect of an AD risk variant (rs7982) in the 5th exon of CLU on alternative splicing by using an integrative approach of brain-tissue-based RNA-Seq and whole genome sequencing data from Accelerating Medicines Partnership—Alzheimer’s Disease (AMP-AD). RNA-Seq data were generated from three regions in the temporal lobe of the brain—the temporal cortex, superior temporal gyrus, and parahippocampal gyrus. The rs7982 was significantly associated with intron retention (IR) of the 5th exon of CLU; as the number of alternative alleles (G) increased, the IR rates decreased more significantly in females than in males. Our results suggest a sex-dependent role of rs7982 in AD pathogenesis via splicing regulation.

scholarly journals Intrinsic Regulatory Role of RNA Structural Arrangement in Alternative Splicing Control

2020 ◽  
Vol 21 (14) ◽  
pp. 5161 ◽  
Author(s):  
Katarzyna Taylor ◽  
Krzysztof Sobczak
Keyword(s):  
Alternative Splicing ◽  
Rna Structure ◽  
The Other ◽  
Splicing Regulation ◽  
Rna Structures ◽  
Structural Arrangement ◽  
Biological Functionality ◽  
Cis And Trans ◽  
Structural Aspects

Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.

scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Computational Analysis ◽  
Potential Role ◽  
Exon Skipping ◽  
Chronic Inflammatory Disease ◽  
Splicing Factors ◽  
The Novel ◽  
Rna Seq ◽  
Genome Wide

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.

scholarly journals Transcriptome profiling reveals transcriptional and alternative splicing regulation in the early embryonic development of hair follicles in the cashmere goat

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yanjun Zhang ◽  
Lele Wang ◽  
Zhen Li ◽  
Dong Chen ◽  
Wenjing Han ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Molecular Mechanisms ◽  
Transcriptome Profiling ◽  
Hair Follicles ◽  
Splicing Regulation ◽  
Cashmere Goat ◽  
Rna Seq ◽  
Three Stages ◽  
Functional Pathways ◽  
First Time

AbstractThe undercoat fiber of the cashmere goat, from the secondary hair follicle (HF), possesses commercial value. However, very few studies have focused on the molecular details of primary and secondary HF initiation and development in goat embryos. In this study, skin samples at embryonic day 45, 55, and 65 (E45, E55, and E65) were collected and prepared for RNA sequencing (RNA-seq). We found that the HF probably initiated from E55 to E65 by analyzing the functional pathways of differentially expressed genes (DEGs). Most key genes in canonical signaling pathways, including WNT, TGF-β, FGF, Hedgehog, NOTCH, and other factors showed clear expression changes from E55 to E65. We, for the first time, explored alternative splicing (AS) alterations, which showed distinct patterns among these three stages. Functional pathways of AS-regulated genes showed connections to HF development. By comparing the published RNA-seq samples from the E60, E120, and newborn (NB) stages, we found the majority of WNT/β-catenin signaling genes were important in the initiation of HF development, while other factors including FOXN1, GATA3, and DLX3 may have a consistent influence on HF development. Our investigation supported the time points of embryonic HF initiation and identified genes that have potential functions of embryonic HF initiation and development. We further explored the potential regulatory roles of AS in HF initiation, which extended our knowledge about the molecular mechanisms of HF development.

scholarly journals KDM3A regulates alternative splicing of cell-cycle genes following DNA damage

2020 ◽  
Author(s):  
Mai Baker ◽  
Mayra Petasny ◽  
Mercedes Bentata ◽  
Gillian Kay ◽  
Eden Engal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Alternative Splicing ◽  
Cell Cycle Regulation ◽  
Splicing Regulation ◽  
Rna Seq ◽  
Cell Cycle Genes ◽  
Cellular Environment ◽  
Demethylase Activity ◽  
Cycle Regulation

ABSTRACTChanges in the cellular environment result in chromatin structure alteration, which in turn regulates gene expression. To learn about the effect of the cellular environment on the transcriptome, we studied the H3K9 de-methylase KDM3A. Using RNA-seq, we found that KDM3A regulates the transcription and alternative splicing of genes associated with cell cycle and DNA damage. We showed that KDM3A undergoes phosphorylation by PKA at serine 265 following DNA damage, and that the phosphorylation is important for a proper cell cycle regulation. We demonstrated that SAT1 alternative splicing, regulated by KDM3A, plays a role in cell cycle regulation. Furthermore we found that KDM3A’s demethylase activity is not needed for SAT1 alternative splicing regulation. In addition, we identified KDM3A’s protein partner ARID1A, the SWI/SNF subunit, and SRSF3 as regulators of SAT1 alternative splicing and showed that KDM3A is essential for SRSF3 binding to SAT1 pre-mRNA. These results suggest that KDM3A serves as a sensor of the environment and an adaptor for splicing factor binding. Our work reveals chromatin sensing of the environment in the regulation of alternative splicing.

scholarly journals Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 188 ◽  
Author(s):  
Liliana Florea ◽  
Li Song ◽  
Steven L Salzberg
Keyword(s):  
Alternative Splicing ◽  
Gene Diversity ◽  
Exon Skipping ◽  
Human Tissues ◽  
Rna Seq ◽  
Gene Splicing ◽  
Link Type ◽  
Normal Human ◽  
Splicing Patterns

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads).  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed (‘switched’) between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository(http://zenodo.org/record/7068; doi:10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.

scholarly journals A Computational Analysis of Alternative Splicing across Mammalian Tissues Reveals Circadian and Ultradian Rhythms in Splicing Events

2019 ◽  
Vol 20 (16) ◽  
pp. 3977 ◽  
Author(s):  
Rukeia El-Athman ◽  
Dora Knezevic ◽  
Luise Fuhr ◽  
Angela Relógio
Keyword(s):  
Alternative Splicing ◽  
Circadian Clock ◽  
Computational Analysis ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Expression Patterns ◽  
Rna Seq ◽  
Ultradian Rhythms ◽  
Mammalian Tissues

Mounting evidence points to a role of the circadian clock in the temporal regulation of post-transcriptional processes in mammals, including alternative splicing (AS). In this study, we carried out a computational analysis of circadian and ultradian rhythms on the transcriptome level to characterise the landscape of rhythmic AS events in published datasets covering 76 tissues from mouse and olive baboon. Splicing-related genes with 24-h rhythmic expression patterns showed a bimodal distribution of peak phases across tissues and species, indicating that they might be controlled by the circadian clock. On the output level, we identified putative oscillating AS events in murine microarray data and pairs of differentially rhythmic splice isoforms of the same gene in baboon RNA-seq data that peaked at opposing times of the day and included oncogenes and tumour suppressors. We further explored these findings using a new circadian RNA-seq dataset of human colorectal cancer cell lines. Rhythmic isoform expression patterns differed between the primary tumour and the metastatic cell line and were associated with cancer-related biological processes, indicating a functional role of rhythmic AS that might be implicated in tumour progression. Our data shows that rhythmic AS events are widespread across mammalian tissues and might contribute to a temporal diversification of the proteome.

scholarly journals Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 188 ◽  
Author(s):  
Liliana Florea ◽  
Li Song ◽  
Steven L Salzberg
Keyword(s):  
Alternative Splicing ◽  
Gene Diversity ◽  
Exon Skipping ◽  
Human Tissues ◽  
Rna Seq ◽  
Gene Splicing ◽  
Link Type ◽  
Normal Human ◽  
Splicing Patterns

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads).  Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed (‘switched’) between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared.  Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository(http://zenodo.org/record/7068; doi:10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.

scholarly journals SYMPK Is Required for Meiosis and Involved in Alternative Splicing in Male Germ Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Rui Wu ◽  
Junfeng Zhan ◽  
Bo Zheng ◽  
Zhen Chen ◽  
Jianbo Li ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Germ Cells ◽  
Strand Break ◽  
Rna Seq ◽  
Male Germ Cells ◽  
Meiotic Progression ◽  
Chromosome Synapsis ◽  
Dna Double Strand Break ◽  
Nascent Transcripts

SYMPK is a scaffold protein that supports polyadenylation machinery assembly on nascent transcripts and is also involved in alternative splicing in some mammalian somatic cells. However, the role of SYMPK in germ cells remains unknown. Here, we report that SYMPK is highly expressed in male germ cells, and germ cell-specific knockout (cKO) of Sympk in mouse leads to male infertility. Sympk cKODdx4–cre mice showed reduced spermatogonia at P4 and almost no germ cells at P18. Sympk cKOStra8–Cre spermatocytes exhibit defects in homologous chromosome synapsis, DNA double-strand break (DSB) repair, and meiotic recombination. RNA-Seq analyses reveal that SYMPK is associated with alternative splicing, besides regulating the expressions of many genes in spermatogenic cells. Importantly, Sympk deletion results in abnormal alternative splicing and a decreased expression of Sun1. Taken together, our results demonstrate that SYMPK is pivotal for meiotic progression by regulating pre-mRNA alternative splicing in male germ cells.

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