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International Journal of Molecular... Oct 2020organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of... (Review)
Review
organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of the most intriguing aspects of the brucellae is that the various species show a ~97% similarity at the genome level. Still, the distinct species display different host preferences, zoonotic risk, and virulence. After 133 years of research, there are many aspects of the biology that remain poorly understood, such as host adaptation and virulence mechanisms. A strategy to understand these characteristics focuses on the relationship between the genomic diversity and host preference of the various species. Pseudogenization, genome reduction, single nucleotide polymorphism variation, number of tandem repeats, and mobile genetic elements are unveiled markers for host adaptation and virulence. Understanding the mechanisms of genome variability in the genus is relevant to comprehend the emergence of pathogens.
Topics: Animals; Brucella; Brucellosis; Evolution, Molecular; Genome, Bacterial; Genomics; Humans; Phylogeny; Polymorphism, Single Nucleotide; Virulence
PubMed: 33092044
DOI: 10.3390/ijms21207749 -
Nature Oct 2023Scientists have been trying to identify every gene in the human genome since the initial draft was published in 2001. In the years since, much progress has been made in... (Review)
Review
Scientists have been trying to identify every gene in the human genome since the initial draft was published in 2001. In the years since, much progress has been made in identifying protein-coding genes, currently estimated to number fewer than 20,000, with an ever-expanding number of distinct protein-coding isoforms. Here we review the status of the human gene catalogue and the efforts to complete it in recent years. Beside the ongoing annotation of protein-coding genes, their isoforms and pseudogenes, the invention of high-throughput RNA sequencing and other technological breakthroughs have led to a rapid growth in the number of reported non-coding RNA genes. For most of these non-coding RNAs, the functional relevance is currently unclear; we look at recent advances that offer paths forward to identifying their functions and towards eventually completing the human gene catalogue. Finally, we examine the need for a universal annotation standard that includes all medically significant genes and maintains their relationships with different reference genomes for the use of the human gene catalogue in clinical settings.
Topics: Humans; Genome, Human; Molecular Sequence Annotation; Protein Isoforms; Human Genome Project; Genes; Pseudogenes; RNA
PubMed: 37794265
DOI: 10.1038/s41586-023-06490-x -
Methods in Molecular Biology (Clifton,... 2021Pseudogenes have long been considered nonfunctional elements. The influx of large-scale sequencing projects over the last decade have provided rich sources of evidence...
Pseudogenes have long been considered nonfunctional elements. The influx of large-scale sequencing projects over the last decade have provided rich sources of evidence that pseudogenes can play key evolutionary and regulatory roles, highlighting the need for high quality annotation for both human and key model organisms. To date, GENCODE has completed the manual annotation of pseudogenes in human and has undertaken the task to curate and characterize pseudogenes in the mouse reference genome. Capitalizing on available high-quality annotations as well as on the functional-genomics, evolutionary, and phenotypical data, we were able to create a comprehensive picture of both the human and mouse pseudogene complements' creation, development, and activity. Thus, we found that while human pseudogenes were created through a single burst of retrotransposition events, the active transposable element content in mouse allows for a continuous renewal of the pseudogene pool. Despite their differences, the two organisms share a number of similarities in terms of pseudogene activity, with ~10% of pseudogenes being transcribed. Finally, we highlight a variety of resources developed based on the available GENCODE annotations that help shed light on pseudogene biology.
Topics: Animals; Computational Biology; Databases, Genetic; Evolution, Molecular; Genomics; Humans; Mice; Molecular Sequence Annotation; Pseudogenes; Retroelements; Sequence Analysis, DNA; Transcription, Genetic
PubMed: 34165709
DOI: 10.1007/978-1-0716-1503-4_5 -
Nature Communications Mar 2020Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms...
Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.
Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cellular Reprogramming; Esophageal Squamous Cell Carcinoma; Female; Gene Knockout Techniques; Glycolysis; Humans; Mice, Inbred BALB C; Mice, Nude; Phosphofructokinase-2; Pseudogenes; RNA, Long Noncoding; Up-Regulation; Xenograft Model Antitumor Assays
PubMed: 32198345
DOI: 10.1038/s41467-020-15112-3 -
Nucleic Acids Research Jan 2021The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports...
The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.
Topics: Animals; COVID-19; Computational Biology; Databases, Genetic; Epidemics; Genomics; Humans; Internet; Mice; Molecular Sequence Annotation; Pseudogenes; RNA, Long Noncoding; SARS-CoV-2; Transcription, Genetic
PubMed: 33270111
DOI: 10.1093/nar/gkaa1087 -
Nucleic Acids Research Jan 2023Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological...
Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.
Topics: Ferroptosis; Data Accuracy; Databases, Factual; Lipid Peroxidation; Pseudogenes
PubMed: 36305834
DOI: 10.1093/nar/gkac935 -
Methods in Molecular Biology (Clifton,... 2022MicroRNAs (miRNAs) are a class of noncoding RNAs of 17-22 nucleotides in length with a critical function in posttranscriptional gene regulation. These master regulators...
MicroRNAs (miRNAs) are a class of noncoding RNAs of 17-22 nucleotides in length with a critical function in posttranscriptional gene regulation. These master regulators are themselves subject to regulation both transcriptionally and posttranscriptionally. Recently, miRNA function has been shown to be modulated by exogenous RNA molecules that function as miRNA sponges. Interestingly, endogenous transcripts such as transcribed pseudogenes, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and mRNAs may serve as natural miRNA sponges. These transcripts, which bind to miRNAs and competitively sequester them away from their targets, are naturally existing endogenous miRNA sponges, called competing endogenous RNAs (ceRNAs). Here we present a historical background of miRNAs, exogenous and endogenous miRNA sponges as well as some examples of endogenous miRNA sponges involved in regulatory mechanisms associated with various diseases, developmental stages, and other cellular processes.
Topics: Gene Regulatory Networks; MicroRNAs; RNA, Circular; RNA, Long Noncoding; RNA, Messenger; RNA, Untranslated
PubMed: 34432275
DOI: 10.1007/978-1-0716-1170-8_5 -
Nature Sep 2023The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date and led to its systematic omission from genomic...
The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.
Topics: Humans; Male; Chromosomes, Human, Y; Genome, Human; Genomics; Mutation Rate; Phenotype; Evolution, Molecular; Euchromatin; Pseudogenes; Genetic Variation; Chromosomes, Human, X; Pseudoautosomal Regions
PubMed: 37612510
DOI: 10.1038/s41586-023-06425-6 -
Methods in Molecular Biology (Clifton,... 2021Although long thought of as "gene relics," pseudogenes have recently gained research and medical interests because of their potential impacts on cellular pathways and of... (Review)
Review
Although long thought of as "gene relics," pseudogenes have recently gained research and medical interests because of their potential impacts on cellular pathways and of their clinical relevance. Studies have profiled pseudogenes at both DNA and RNA levels in cancers. Differences in pseudogene expression (RNA) or occurrence (DNA) help cancer subtype classification, which in turn can contribute to improving treatment selection in precision medicine. Such differences are also associated with clinical outcomes, such as patient survival.Here we review the existing methods on pseudogene profiling and discuss the application scenarios, as well as their relevant issues and challenges.
Topics: DNA, Neoplasm; Datasets as Topic; Gene Expression Regulation, Neoplastic; Humans; Molecular Sequence Annotation; Multigene Family; Neoplasm Proteins; Neoplasms; Patients; Prognosis; Pseudogenes; RNA, Messenger; RNA, Neoplasm
PubMed: 34165723
DOI: 10.1007/978-1-0716-1503-4_19 -
Frontiers in Molecular Biosciences 2020Cardiovascular disease is the main disease that affects human life span. In recent years, the disease has been increasingly addressed at the molecular levels, for... (Review)
Review
Cardiovascular disease is the main disease that affects human life span. In recent years, the disease has been increasingly addressed at the molecular levels, for example, pseudogenes are now known to be involved in the pathogenesis and development of cardiovascular diseases. Pseudogenes are non-coding homologs of protein-coding genes and were once called "junk gene." Since they are highly homologous to their functional parental genes, it is somewhat difficult to distinguish them. With the development of sequencing technology and bioinformatics, pseudogenes have become readily identifiable. Recent studies indicate that pseudogenes are closely related to cardiovascular diseases. This review provides an overview of pseudogenes and their roles in the pathogenesis of cardiovascular diseases. This new knowledge adds to our understanding of cardiovascular disease at the molecular level and will help develop new biomarkers and therapeutic approaches designed to prevent and treat the disease.
PubMed: 33644114
DOI: 10.3389/fmolb.2020.622540