scholarly journals Not So Dead Genes—Retrocopies as Regulators of Their Disease-Related Progenitors and Hosts

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 912
Author(s):  
Joanna Ciomborowska-Basheer ◽  
Klaudia Staszak ◽  
Magdalena Regina Kubiak ◽  
Izabela Makałowska
Keyword(s):  
Alternative Splicing ◽  
Gene Duplication ◽  
Epigenetic Regulation ◽  
Noncoding Rnas ◽  
Cardiovascular Disorders ◽  
Bioinformatics Analyses ◽  
Molecular Machinery ◽  
Stabilizing Factors ◽  
Host Genes ◽  
Over Time

Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding RNAs (lncRNAs). The mechanisms by which they can regulate other genes include microRNA sponging, modulation of alternative splicing, epigenetic regulation and competition for stabilizing factors, among others. Here, we summarize recent findings related to lncRNAs originating from retrocopies that are involved in human diseases such as cancer and neurodegenerative, mental or cardiovascular disorders. Special attention is given to retrocopies that regulate their progenitors or host genes. Presented evidence from the literature and our bioinformatics analyses demonstrates that these retrocopies, often described as unimportant pseudogenes, are significant players in the cell’s molecular machinery.

scholarly journals Epigenetic Regulation of Dental Pulp Stem Cell Fate

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Dan Zhou ◽  
Lu Gan ◽  
Yiran Peng ◽  
Yachuan Zhou ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Dental Pulp ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Stem Cell Fate ◽  
The Past ◽  
Multipotent Differentiation ◽  
Dental Pulp Stem Cell

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.

scholarly journals Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1498 ◽  
Author(s):  
Elisa Belloni ◽  
Anna Di Matteo ◽  
Davide Pradella ◽  
Margherita Vacca ◽  
Christopher D. R. Wyatt ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Protein Isoforms ◽  
Peroxisome Proliferator ◽  
Bioinformatics Analyses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Significant Enrichment ◽  
Steady State Levels

Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology.

scholarly journals Epigenetic Regulation in Hepatocellular Carcinoma Requires Long Noncoding RNAs

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Amicone ◽  
Franca Citarella ◽  
Carla Cicchini
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epigenetic Regulation ◽  
Tumor Suppressors ◽  
Biological Significance ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Therapeutic Approaches ◽  
Adult Liver ◽  
Liver Malignancy ◽  
Epigenetic Modifiers

Recent evidence has proven the relevance of epigenetic changes in the development of hepatocellular carcinoma (HCC), the major adult liver malignancy. Moreover, HCC onset and progression correlate with the deregulation of several long noncoding RNAs (lncRNAs), exhibiting great biological significance. As discussed in this review, many of these transcripts are able to specifically act as tumor suppressors or oncogenes by means of their role as molecular platforms. Indeed, these lncRNAs are able to bind and recruit epigenetic modifiers on specific genomic loci, ultimately resulting in regulation of the gene expression relevant in cancer development. The evidence presented in this review highlights that lncRNAs-mediated epigenetic regulation should be taken into account for potential targeted therapeutic approaches.

scholarly journals An Arabidopsis long noncoding RNA modulates the transcriptome through interactions with a network of splicing factors

2020 ◽  
Author(s):  
Richard Rigo ◽  
Jérémie Bazin ◽  
Natali Romero-Barrios ◽  
Michaël Moison ◽  
Leandro Lucero ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Root Formation ◽  
Noncoding Rnas ◽  
Dynamic Network ◽  
Splicing Factors ◽  
Genome Wide ◽  
A Minor ◽  
Conserved Core

ABSTRACTAlternative splicing (AS) is a major source of transcriptome and proteome diversity in higher organisms. Long noncoding RNAs (lncRNAs) have emerged as regulators of AS through a range of molecular mechanisms. In Arabidopsis thaliana, the AS regulators NSRa and b, which affect auxin-driven lateral root formation, can interact with the ALTERNATIVE SPLICING COMPETITOR (ASCO) lncRNA. Here, we analyzed the effect of the knockdown and overexpression of ASCO at genome-wide level and found a high number of deregulated and differentially spliced genes, related to flagellin responses and biotic stress. In agreement, roots from ASCO-knocked down plants are more sensitive to flagellin. Surprisingly, only a minor subset of genes overlapped with the AS defects of the nsra/b double mutant. Using biotin-labelled oligonucleotides for RNA-mediated ribonucleoprotein purification, we found that ASCO binds to the highly conserved core spliceosome component PRP8a. ASCO deregulation impairs the recognition of specific flagellin-related transcripts by PRP8a and SmD1b, another spliceosome component, suggesting that ASCO function regulates AS through the interaction with multiple splicing factors. Hence, lncRNAs may interact in a dynamic network with many splicing factors to modulate transcriptome reprogramming in eukaryotes.

scholarly journals Systematic Profiling of Survival-Associated Alternative Splicing Events in Adrenocortical Carcinoma

2020 ◽  
Author(s):  
Xia Fang ◽  
Qin Wan ◽  
Yang Long ◽  
Fangyuan Teng ◽  
Xiaozhen Tan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Predictive Models ◽  
Adrenocortical Carcinoma ◽  
Clinical Information ◽  
Splicing Factor ◽  
Lasso Regression ◽  
Bioinformatics Analyses ◽  
Systematic Analysis ◽  
Underlying Mechanisms ◽  
Cox Analysis

Abstract Background: Aberrant alternative splicing (AS) is involved in many oncogenic processes and systematic analysis of survival-associated aberrant AS events has been reported in many cancers. This study aims to systematic profiling the AS signature in Adrenocortical carcinoma (ACC).Methods: Data of ACC were downloaded from TCGA and TCGA SpliceSeq. Clinical information and AS events data were integrated with the same TCGA ID. Then, we performed univariate Cox analysis to identify survival-related AS events. Lasso regression and multivariate Cox analysis were used to establish prognostic model. In addition, several bioinformatics analyses were conducted to identify pathways enriched by genes of survival-associated AS events and construct splicing-factor-regulated network.Results: A total of 77 patients with complete clinical information and PSI values of AS events were included in the present study. We detected 3781 AS events in 2366 genes were associated with overall survival of ACC patients. All the predictive models showed efficiency in distinguishing good and poor outcomes of ACC patients. All the AUCs of predictive models were greater than 0.7. Functional analysis genes with survival-associated AS events suggested that the POLR2H, TCEB2, PSMA1, PSMD11 and SKP2 ranked at the core. The splicing-factor-regulated network revealed the potential regulatory mechanisms of AS events in ACC.Conclusions: Our systematic profiling of survival-associated AS events in ACC patients provides novel molecular alternations and contributes to decipher the underlying mechanisms of AS in oncogenesis of ACC.

scholarly journals Conservation of mRNA quality control factor Ski7 and its diversification through changes in alternative splicing and gene duplication

2018 ◽  
Vol 115 (29) ◽  
pp. E6808-E6816 ◽  
Author(s):  
Alexandra N. Marshall ◽  
Jaeil Han ◽  
Minseon Kim ◽  
Ambro van Hoof
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Alternative Splicing ◽  
Gene Duplication ◽  
Transcriptome Analysis ◽  
Control Factor ◽  
Intrinsically Disordered ◽  
Alternatively Spliced ◽  
Rna Exosome ◽  
Close Relatives

Eukaryotes maintain fidelity of gene expression by preferential degradation of aberrant mRNAs that arise by errors in RNA processing reactions. In Saccharomyces cerevisiae, Ski7 plays an important role in this mRNA quality control by mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be restricted to Saccharomyces cerevisiae and close relatives because the SKI7 gene and its paralog HBS1 arose by whole genome duplication (WGD) in a recent ancestor. We have recently shown that the preduplication gene was alternatively spliced and that Ski7 function predates WGD. Here, we use transcriptome analysis of diverse eukaryotes to show that diverse eukaryotes use alternative splicing of SKI7/HBS1 to encode two proteins. Although alternative splicing affects the same intrinsically disordered region of the protein, the pattern of splice site usage varies. This alternative splicing event arose in an early eukaryote that is a common ancestor of plants, animals, and fungi. Remarkably, through changes in alternative splicing and gene duplication, the Ski7 protein has diversified such that different species express one of four distinct Ski7-like proteins. We also show experimentally that the Saccharomyces cerevisiae SKI7 gene has undergone multiple changes that are incompatible with the Hbs1 function and may also have undergone additional changes to optimize mRNA quality control. The combination of transcriptome analysis in diverse eukaryotes and genetic analysis in yeast clarifies the mechanism by which a Ski7-like protein is expressed across eukaryotes and provides a unique view of changes in alternative splicing patterns of one gene over long evolutionary time.

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