Taking the pseudo out of pseudogenes

Goodhead, Ian; Darby, Alistair C.

doi:10.1016/j.mib.2014.11.012

Cited by 69 publications

(65 citation statements)

References 67 publications

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“…8,9 Although pseudogenes were considered as non-functional genomics fossils or biologically inconsequential for a long time, recent studies have revealed that they actually play critical roles in post-transcriptional or transcriptional regulation of gene expression by functioning as endogenous competitors for microRNA (miRNA) or RNA-binding protein (RBP), and endogenous small interfering RNA (endo-siRNA or esiRNA). [10][11][12][13][14][15] Interestingly, increasing evidence has indicated that some pseudogenes play critical roles in human diseases, especially cancer. [16][17][18] For example, Poliseno et al 19,20 reported that the pseudogene PTENP1 functions in regulating PTEN by acting as a decoy for PTEN-related miRNAs such as miR-17, miR-21, miR-214, miR-19, and miR-26.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

et al. 2017

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“…Intriguingly, in E. coli K-12 two gene classes exist, which together comprise more than 225 genes (∼5% of the total gene pool), with no apparent function at all (Keseler et al, 2013). These are Phantom-genes, which have been identified as genes through computational searches, but without any observed expression, and Pseudo-genes, which are genes with homology to functionally expressed genes, but with changes in their sequences that prevent expression (Keseler et al, 2013; Goodhead and Darby, 2015). The widespread appearance of such genes might indicate that they are not subject to deselection even though they are redundant.…”

Section: The Evolving Nucleoidmentioning

confidence: 99%

Impact of Chromosomal Architecture on the Function and Evolution of Bacterial Genomes

2018

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The bacterial nucleoid is highly condensed and forms compartment-like structures within the cell. Much attention has been devoted to investigating the dynamic topology and organization of the nucleoid. In contrast, the specific nucleoid organization, and the relationship between nucleoid structure and function is often neglected with regard to importance for adaption to changing environments and horizontal gene acquisition. In this review, we focus on the structure-function relationship in the bacterial nucleoid. We provide an overview of the fundamental properties that shape the chromosome as a structured yet dynamic macromolecule. These fundamental properties are then considered in the context of the living cell, with focus on how the informational flow affects the nucleoid structure, which in turn impacts on the genetic output. Subsequently, the dynamic living nucleoid will be discussed in the context of evolution. We will address how the acquisition of foreign DNA impacts nucleoid structure, and conversely, how nucleoid structure constrains the successful and sustainable chromosomal integration of novel DNA. Finally, we will discuss current challenges and directions of research in understanding the role of chromosomal architecture in bacterial survival and adaptation.

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“…Interestingly, a number of pseudogenes identified through DNA sequencing technologies possessing premature stop codons have been found to translate biologically important functional proteins due to translational read-through of the predicted stop codon [105]. As with other aspects of genome biology, computational analysis is predictive, and functional studies are crucial for thorough understanding.…”

Section: Pseudogenesmentioning

confidence: 99%

“…The first de novo evidence that retrotransposition could lead to constitutional genetic defects causing human disease came from studies in hemophilia [105]. The first of these indicated 2 of 240 examined hemophilia A patients’ insertions of LINEs positioned within exon 14 of the coagulation factor VIII gene [112].…”

Section: Retrotransposonsmentioning

confidence: 99%

“…Despite the high incidence of leukemias, lymphomas and myelomas (about 10% cancer diagnosed) the role of retrotransposon elements as inherited predisposing factors or somatic mutagens is under explored [105]. Loss of DNA methylation and retrotransposon integration into clinically sensitive genes has been reported in CLL [122, 123], multiple myeloma (MM) [124].…”

Section: Retrotransposonsmentioning

confidence: 99%

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Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

Wilkes

Repellin

Sakamoto

2017

Molecular Genetics and Metabolism

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The role of non-coding Ribonucleic Acids (ncRNAs) in biology is currently an area of intense focus. Hematopoiesis requires rapidly changing regulatory molecules to guide appropriate differentiation and ncRNA are well suited for this. It is not surprising that virtually all aspects of hematopoiesis have roles for ncRNAs assigned to them and doubtlessly much more await characterization. Stem cell maintenance, lymphoid, myeloid and erythroid differentiation are all regulated by various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and various transposable elements within the genome. As our understanding of the many and complex ncRNA roles continues to grow, new discoveries are challenging the existing classification schemes. In this review we briefly overview the broad categories of ncRNAs and discuss a few examples regulating normal and aberrant hematopoiesis.

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Taking the pseudo out of pseudogenes

Cited by 69 publications

References 67 publications

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

RETRACTED: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

Impact of Chromosomal Architecture on the Function and Evolution of Bacterial Genomes

Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

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