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Plant Signaling & Behavior 2019Pseudogenes, nonfunctional genomic sequences derived from functional protein-coding genes, form by duplication or retrotransposition, and loss of gene function by...
Pseudogenes, nonfunctional genomic sequences derived from functional protein-coding genes, form by duplication or retrotransposition, and loss of gene function by disabling mutations. Studies on the evolution and functional aspects of plant pseudogenes are limited, despite their abundance in the plant genome. To date, most researches on pseudogenes focus on mammals. Here, we summarized current knowledge on pseudogenes including the historical and recent progress, analyzes their essential roles in gene regulation in hope of further stimulating researches in plant species for understanding gene regulation and evolution.
Topics: Animals; Evolution, Molecular; Gene Expression Regulation; Genome, Plant; Humans; Mutation; Pseudogenes
PubMed: 31161861
DOI: 10.1080/15592324.2019.1625698 -
The International Journal of... Sep 2014A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may... (Review)
Review
A paradigm shift is sweeping modern day molecular biology following the realisation that large amounts of "junk" DNA", thought initially to be evolutionary remnants, may actually be functional. Several recent studies support a functional role for pseudogene-expressed non-coding RNAs in regulating their protein-coding counterparts. Several hundreds of pseudogenes have been reported as transcribed into RNA in a large variety of tissues and tumours. Most studies have focused on pseudogenes expressed in the sense direction, but some reports suggest that pseudogenes can also be transcribed as antisense RNAs (asRNAs). A few examples of key regulatory genes, such as PTEN and OCT4, have in fact been reported to be under the regulation of pseudogene-expressed asRNAs. Here, we review what are known about pseudogene expressed non-coding RNA mediated gene regulation and their roles in the control of epigenetic states. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.
Topics: Animals; Epigenomics; Gene Expression Regulation; Humans; Pseudogenes; RNA, Antisense; RNA, Long Noncoding; Transcription, Genetic
PubMed: 24842102
DOI: 10.1016/j.biocel.2014.05.008 -
Nature Communications Mar 2020Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level....
Pseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes Ub (Q2K, K33E, Q49K, N60S). The functional consequences of Ub conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that Ub modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.
Topics: CRISPR-Cas Systems; Cell Division; Cell Nucleus; Cloning, Molecular; Datasets as Topic; Gene Knockout Techniques; HEK293 Cells; HeLa Cells; Humans; Lamin Type A; Proteomics; Pseudogenes; RNA-Seq; Ubiquitin; Ubiquitination
PubMed: 32161257
DOI: 10.1038/s41467-020-15090-6 -
Pacific Symposium on Biocomputing.... 2018Pseudogenes are fossil relatives of genes. Pseudogenes have long been thought of as "junk DNAs", since they do not code proteins in normal tissues. Although most of the...
Pseudogenes are fossil relatives of genes. Pseudogenes have long been thought of as "junk DNAs", since they do not code proteins in normal tissues. Although most of the human pseudogenes do not have noticeable functions, ∼20% of them exhibit transcriptional activity. There has been evidence showing that some pseudogenes adopted functions as lncRNAs and work as regulators of gene expression. Furthermore, pseudogenes can even be "reactivated" in some conditions, such as cancer initiation. Some pseudogenes are transcribed in specific cancer types, and some are even translated into proteins as observed in several cancer cell lines. All the above have shown that pseudogenes could have functional roles or potentials in the genome. Evaluating the relationships between pseudogenes and their gene counterparts could help us reveal the evolutionary path of pseudogenes and associate pseudogenes with functional potentials. It also provides an insight into the regulatory networks involving pseudogenes with transcriptional and even translational activities.In this study, we develop a novel approach integrating graph analysis, sequence alignment and functional analysis to evaluate pseudogene-gene relationships, and apply it to human gene homologs and pseudogenes. We generated a comprehensive set of 445 pseudogene-gene (PGG) families from the original 3,281 gene families (13.56%). Of these 438 (98.4% PGG, 13.3% total) were non-trivial (containing more than one pseudogene). Each PGG family contains multiple genes and pseudogenes with high sequence similarity. For each family, we generate a sequence alignment network and phylogenetic trees recapitulating the evolutionary paths. We find evidence supporting the evolution history of olfactory family (both genes and pseudogenes) in human, which also supports the validity of our analysis method. Next, we evaluate these networks in respect to the gene ontology from which we identify functions enriched in these pseudogene-gene families and infer functional impact of pseudogenes involved in the networks. This demonstrates the application of our PGG network database in the study of pseudogene function in disease context.
Topics: Chromosome Mapping; Computational Biology; Conserved Sequence; DNA, Intergenic; Databases, Genetic; Evolution, Molecular; Gene Ontology; Gene Regulatory Networks; Humans; Markov Chains; Models, Genetic; Multigene Family; Phylogeny; Pseudogenes; Sequence Alignment; Smell
PubMed: 29218912
DOI: No ID Found -
Nature Communications Jun 2021Transposable elements (TEs) help shape the structure and function of the human genome. When inserted into some locations, TEs may disrupt gene regulation and cause...
Transposable elements (TEs) help shape the structure and function of the human genome. When inserted into some locations, TEs may disrupt gene regulation and cause diseases. Here, we present xTea (x-Transposable element analyzer), a tool for identifying TE insertions in whole-genome sequencing data. Whereas existing methods are mostly designed for short-read data, xTea can be applied to both short-read and long-read data. Our analysis shows that xTea outperforms other short read-based methods for both germline and somatic TE insertion discovery. With long-read data, we created a catalogue of polymorphic insertions with full assembly and annotation of insertional sequences for various types of retroelements, including pseudogenes and endogenous retroviruses. Notably, we find that individual genomes have an average of nine groups of full-length L1s in centromeres, suggesting that centromeres and other highly repetitive regions such as telomeres are a significant yet unexplored source of active L1s. xTea is available at https://github.com/parklab/xTea .
Topics: DNA Transposable Elements; Gene Rearrangement; Genetic Variation; Genome, Human; Genomics; Haplotypes; Humans; Molecular Sequence Annotation; Mutagenesis, Insertional; Pseudogenes; Whole Genome Sequencing
PubMed: 34158502
DOI: 10.1038/s41467-021-24041-8 -
Scientific Reports Dec 2023Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The present study explored the potential role of pseudogenes in BC via construction...
Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The present study explored the potential role of pseudogenes in BC via construction and analysis of a competing endogenous RNA (ceRNA) network through a three-step process. First, we screened differentially expressed genes in nine BC datasets. Then the gene-pseudogenes pairs (nine hub genes) were selected according to the functional enrichment and correlation analysis. Second, the candidate hub genes and interacting miRNAs were used to construct the ceRNA network. Further analysis of the ceRNA network revealed a crucial ceRNA module with two genes-pseudogene pairs and two miRNAs. The in-depth analysis identified the GBP1/hsa-miR-30d-5p/GBP1P1 axis as a potential tumorigenic axis in BC patients. In the third step, the GBP1/hsa-miR-30d-5p/GBP1P1 axis expression level was assessed in 40 tumor/normal BC patients and MCF-7 cell lines. The expression of GBP1 and GBP1P1 was significantly higher in the tumor compared to the normal tissue. However, the expression of hsa-miR-30d-5p was lower in tumor samples. Then, we introduced the GBP1P1 pseudogene into the MCF-7 cell line to evaluate its effect on GBP1 and hsa-miR-30d-5p expression. As expected, the GBP1 level increased while the hsa-miR-30d-5p level decreased in the GBP1P1-overexprsssing cell line. In addition, the oncogenic properties of MCF-7 (cell viability, clonogenicity, and migration) were improved after GBP1P1 overexpression. In conclusion, we report a ceRNA network that may provide new insight into the role of pseudogenes in BC development.
Topics: Humans; Female; Breast Neoplasms; Pseudogenes; RNA, Competitive Endogenous; MicroRNAs; MCF-7 Cells
PubMed: 38072995
DOI: 10.1038/s41598-023-49110-4 -
BMC Cancer Apr 2021Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor, and more than 70% of new cases are in East and Southeast Asia. However, association between NPC and pseudogenes playing important roles in genesis of multiple tumor types is still not clear and needs to be investigated.
METHODS
Using RNA-Sequencing (RNA-seq) technology, we analyzed pseudogene expression in 13 primary NPC and 6 recurrent NPC samples as well as their paracancerous counterparts. Quantitative PCR was used to validate the differentially expressed pseudogenes.
RESULTS
We found 251 differentially expressed pseudogenes including 73 up-regulated and 178 down-regulated ones between primary NPC and paracancerous tissues. Enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted to filter out the key pseudogenes. We reported that pseudogenes from cytochrome P450 (CYP) family, such as CYP2F2P, CYP2G1P, CYP4F24P, CYP2B7P and CYP2G2P were significantly down-regulated in NPC compared to paracancerous tissues, while IGHV1OR15-2, IGHV3-11, FCGR1CP and IGHV3-69-1 belonging to Fc gamma receptors were significantly up-regulated. CYP2B7P, CYP2F2P and CYP4F26P were enriched in arachidonic acid metabolism pathway. The qRT-PCR analysis validated the lower expression of pseudogenes CYP2F2P and CYP2B7P in NPC tissues and cell lines compared to paracancerous tissues and normal human nasopharyngeal epithelial cell line. CYP2B7P overexpression weakened migratory and invasive capacity of NPC cell line. Moreover, the expression pattern of those pseudogenes in recurrent NPC tissues was different from the primary NPC.
CONCLUSION
This study suggested the role of pseudogenes in tumorigenesis and progression, potentially functioning as therapeutic targets to NPC.
Topics: Adult; Aged; Arachidonic Acid; Cell Line, Tumor; Cell Movement; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 2; Down-Regulation; Female; Gene Ontology; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pseudogenes; Real-Time Polymerase Chain Reaction; Receptors, IgG; Sequence Analysis, RNA; Transfection; Up-Regulation
PubMed: 33931030
DOI: 10.1186/s12885-021-08211-x -
Scientific Reports Dec 2022Pseudogene-derived transcripts, especially those barely transcribed in normal tissues, have been regarded as a kind of non-coding RNAs, and present potential functions...
Pseudogene-derived transcripts, especially those barely transcribed in normal tissues, have been regarded as a kind of non-coding RNAs, and present potential functions in tumorigenicity and tumor development in human beings. However, their exact effects on hepatocellular carcinoma (HCC) remain largely unknown. On basis of our previous research and the constructed online database for the non-coding RNAs related to HCC, a series of pseudogene transcripts have been discovered, and SNRPFP1, the homologous pseudogene of SNRPF, was found to produce an anomalously high expression long non-coding RNA in HCC. In this study, we validated the expression of the SNRPFP1 transcript in both HCC tissues and cell lines. The adverse correlation between SNRPFP1 expression and patients' outcomes was observed. And depletion of SNRPF1 in HCC cells significantly suppressed cell proliferation and apoptosis resistance. Meanwhile, the motility of HCC cells was potently impaired. Interestingly, miR-126-5p, one of the tumor-suppressive genes commonly decreased in HCC, was found negatively expressed and correlated with SNRPF1, and a specific region of SNRPF1 transcript is directly binding to miR-126-5p in a molecular sponge way. The rescue experiment by knock-out miR-126-5p significantly reversed the cell growth suppression and a higher ratio of cell apoptosis induced by SNRPF1 depletion. Lastly, we concluded that SNRPF1 is a pseudogene active in HCC, and its abnormally over-expressed transcript is a strong promoter of HCC cell progress in vitro by sponging miR-126-5p. We believe that the findings in this study provide new strategies for HCC prevention and therapeutic treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Long Noncoding; MicroRNAs; Pseudogenes; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Cell Movement
PubMed: 36535956
DOI: 10.1038/s41598-022-24597-5 -
ELife Apr 2020The partial success of a study to reproduce experiments that linked pseudogenes and cancer proves that understanding RNA networks is more complicated than expected.
The partial success of a study to reproduce experiments that linked pseudogenes and cancer proves that understanding RNA networks is more complicated than expected.
Topics: Biology; Humans; Neoplasms; Pseudogenes; RNA; RNA, Messenger; Reproducibility of Results
PubMed: 32314733
DOI: 10.7554/eLife.56397 -
Neoplasia (New York, N.Y.) Oct 2019We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the...
We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (<50 years) with prostate cancer. Screening of patient urine samples showed that KLK4-KLKP1 can be detected noninvasively in urine. Taken together, we present KLK4-KLKP1 as a class of pseudogene associated fusion transcript in cancer with potential applications as a biomarker for routine screening of prostate cancer.
Topics: Amino Acid Sequence; Animals; Cell Line, Tumor; Chick Embryo; Gene Expression Regulation, Neoplastic; Gene Fusion; Genetic Loci; Humans; Kallikreins; Male; Neoplasm Grading; Oncogene Proteins, Fusion; Prostatic Neoplasms; Pseudogenes; Tissue Kallikreins
PubMed: 31446281
DOI: 10.1016/j.neo.2019.07.010