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Veterinary Immunology and... Jun 2024Interferon lambda (IFN-λ) is an important type III interferon triggered mainly by viral infection. IFN-λ binds to their heterodimeric receptors and signals through...
Interferon lambda (IFN-λ) is an important type III interferon triggered mainly by viral infection. IFN-λ binds to their heterodimeric receptors and signals through JAK-STAT pathways similar to type I IFN. In this study, we deduced the buffalo IFN-λ sequences through the polymerase chain reaction, and then studied IFN-λ's expression patterns in different tissues, and post induction with poly I:C and live MRSA using RT-qPCR. The full-length sequences of buffalo IFN-λ3, IFN-λ receptors, and a transcript variant of IFN-λ4 were determined. IFN-λ1 is identified as a pseudogene. Virus response elements and a recombination hotspot factor was observed in the regulatory region of IFN-λ. The IFN-λ3 expressed highest in lungs and monocytes but IFN-λ4 did not. The expression of Interferon Lambda Receptor 1 was tissue specific, while Interleukin 10 Receptor subunit beta was ubiquitous. Following poly I:C induction, IFN-λ3 expression was primarily observed in epithelial cells as opposed to fibroblasts, displaying cell type-dependent expression. The cytosolic RNA sensors were expressed highest in endometrial epithelial cells, whereas the endosomal receptor was higher in fibroblasts. 2',5'-oligoadenylate synthetase expressed higher in fibroblasts, myxoma resistance protein 1 and IFN-stimulated gene 56 in epithelial cells, displaying cell-specific antiviral response of the interferon stimulated genes (ISGs). The endometrial epithelial cells expressed IFN-λ3 after live S. aureus infection indicating its importance in bacterial infection. The induction of IFN-λ3 was S. aureus isolate specific at the same multiplicity of infection (MOI). This study elucidates the IFN-λ sequences, diverse expression patterns revealing tissue specificity, and specificity in response to poly I:C and bacterial stimuli, emphasising its crucial role in innate immune response modulation.
Topics: Animals; Buffaloes; Interferons; Poly I-C; Gene Expression Profiling; Phylogeny; Interferon Lambda; Amino Acid Sequence; Receptors, Interferon; Female; 2',5'-Oligoadenylate Synthetase; Staphylococcus aureus
PubMed: 38735115
DOI: 10.1016/j.vetimm.2024.110770 -
Applied Microbiology and Biotechnology May 2024Pseudogenes are defined as "non-functional" copies of corresponding parent genes. The cognition of pseudogenes continues to be refreshed through accumulating and... (Review)
Review
Pseudogenes are defined as "non-functional" copies of corresponding parent genes. The cognition of pseudogenes continues to be refreshed through accumulating and updating research findings. Previous studies have predominantly focused on mammals, but pseudogenes have received relatively less attention in the field of microbiology. Given the increasing recognition on the importance of pseudogenes, in this review, we focus on several aspects of microorganism pseudogenes, including their classification and characteristics, their generation and fate, their identification, their abundance and distribution, their impact on virulence, their ability to recombine with functional genes, the extent to which some pseudogenes are transcribed and translated, and the relationship between pseudogenes and viruses. By summarizing and organizing the latest research progress, this review will provide a comprehensive perspective and improved understanding on pseudogenes in microorganisms. KEY POINTS: • Concept, classification and characteristics, identification and databases, content, and distribution of microbial pseudogenes are presented. • How pseudogenization contribute to pathogen virulence is highlighted. • Pseudogenes with potential functions in microorganisms are discussed.
Topics: Pseudogenes; Bacteria; Virulence; Viruses
PubMed: 38717672
DOI: 10.1007/s00253-023-12971-w -
Analytical Cellular Pathology... 2024Preeclampsia (PE) manifests as a pregnancy-specific complication arising from compromised placentation characterized by inadequate trophoblast invasion. A growing body...
Preeclampsia (PE) manifests as a pregnancy-specific complication arising from compromised placentation characterized by inadequate trophoblast invasion. A growing body of evidence underscores the pivotal involvement of pseudogenes, a subset of long noncoding RNAs, in the pathological processes of PE. This study presents a novel finding, demonstrating a significant downregulation of the pseudogene PDIA3P1 in PE placental tissues compared to normal tissues. In vitro functional assays revealed that suppressing PDIA3P1 hindered trophoblast proliferation, invasion, and migration, concurrently upregulating the expression of secreted frizzled-related protein 1 (SFRP1). Further exploration of the regulatory role of PDIA3P1 in PE, utilizing human trophoblasts, established that PDIA3P1 exerts its function by binding to HuR, thereby enhancing the stability of Snail expression in trophoblasts. Overall, our findings suggest a crucial role for PDIA3P1 in regulating trophoblast properties and contributing to the pathogenesis of PE, offering potential targets for prognosis and therapeutic intervention.
Topics: Adult; Female; Humans; Pregnancy; Cell Movement; Cell Proliferation; Down-Regulation; Phenotype; Pre-Eclampsia; RNA, Long Noncoding; Snail Family Transcription Factors; Trophoblasts
PubMed: 38715918
DOI: 10.1155/2024/8972022 -
Research Square Apr 2024Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T)...
Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T) Y chromosomes for these species. The pseudo-autosomal regions were similar in length, but the total chromosome size was substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity was accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 18MYA. The centromeres also differed dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosome have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.
PubMed: 38712074
DOI: 10.21203/rs.3.rs-4033388/v1 -
Cancer Diagnosis & Prognosis 2024In the dynamic landscape of hepatocellular carcinoma (HCC) or the liver cancer research, pseudogenes have emerged from the shadows of genetic obscurity to become central... (Review)
Review
In the dynamic landscape of hepatocellular carcinoma (HCC) or the liver cancer research, pseudogenes have emerged from the shadows of genetic obscurity to become central figures, significantly influencing the disease molecular development and clinical trajectory. This review explores a transformative shift in perspective, recognizing pseudogenes not as genetic remnants without function, but as critical regulators in the molecular underpinnings of HCC. Engaging in complex interactions such as microRNA sponging, gene expression modulation, and signaling pathway disruptions, pseudogenes orchestrate a part of the molecular complexity driving tumor genesis, progression, and drug resistance in the liver cancer. Their unique expression patterns in hepatoma tissues herald new opportunities for early HCC detection, offering insights into patient prognosis, and identifying novel targets for therapeutic intervention of this disease. Such advancements underscore the importance of pseudogenes in enriching our understanding and management of HCC, paving the way for more effective diagnostic strategies and targeted therapies in the ongoing battle against this challenging malignancy.
PubMed: 38707729
DOI: 10.21873/cdp.10311 -
The American Journal of Pathology May 2024A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this...
A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs, pseudogenes, and circular RNAs, as well as RNAs denoted as miscellaneous RNAs, was profiled by total RNA sequencing. In addition to well-known coding and noncoding RNAs, differential expression analysis also uncovered transcripts that have not been implicated previously in colon cancer, such as RNA5SP149, RNU4-2, and SNORD3A. Moreover, there was a profound global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in more advanced tumors. A global down-regulation of circular RNAs in tumors relative to normal tissues was observed, although only a few were expressed differentially between tumor stages. Many previously undescribed transcripts, including RNU6-620P, RNU2-20P, VTRNA1-3, and RNA5SP60, indicated strong prognostic biomarker potential in receiver operating characteristics analyses. In summary, this study unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colon cancer. Notably, there was a significant global up-regulation of snRNA pseudogenes, snoRNAs, and rRNA pseudogenes in advanced tumors. Many of these newly discovered candidates demonstrate a strong prognostic potential for stage II colon cancer.
PubMed: 38704091
DOI: 10.1016/j.ajpath.2024.04.003 -
Proceedings of the National Academy of... May 2024Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated...
Ovarian cancer is an aggressive gynecological tumor characterized by a high relapse rate and chemoresistance. Ovarian cancer exhibits the cancer hallmark of elevated glycolysis, yet effective strategies targeting cancer cell metabolic reprogramming to overcome therapeutic resistance in ovarian cancer remain elusive. Here, we revealed that epigenetic silencing of Otubain 2 () is a driving force for mitochondrial metabolic reprogramming in ovarian cancer, which promotes tumorigenesis and chemoresistance. Mechanistically, OTUB2 silencing destabilizes sorting nexin 29 pseudogene 2 (SNX29P2), which subsequently prevents hypoxia-inducible factor-1 alpha (HIF-1α) from von Hippel-Lindau tumor suppressor-mediated degradation. Elevated HIF-1α activates the transcription of carbonic anhydrase 9 () and drives ovarian cancer progression and chemoresistance by promoting glycolysis. Importantly, pharmacological inhibition of CA9 substantially suppressed tumor growth and synergized with carboplatin in the treatment of -silenced ovarian cancer. Thus, our study highlights the pivotal role of OTUB2/SNX29P2 in suppressing ovarian cancer development and proposes that targeting CA9-mediated glycolysis is an encouraging strategy for the treatment of ovarian cancer.
Topics: Female; Ovarian Neoplasms; Humans; Mitochondria; Carbonic Anhydrase IX; Cell Line, Tumor; Animals; Mice; Antigens, Neoplasm; Hypoxia-Inducible Factor 1, alpha Subunit; Glycolysis; Gene Silencing; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; Metabolic Reprogramming
PubMed: 38701117
DOI: 10.1073/pnas.2315348121 -
MedRxiv : the Preprint Server For... Apr 2024Insertion of active retroelements-L1s, s, and SVAs-can disrupt proper genome function and lead to various disorders including cancer. However, the role of retroelements...
Insertion of active retroelements-L1s, s, and SVAs-can disrupt proper genome function and lead to various disorders including cancer. However, the role of retroelements (DNRTs) in birth defects and childhood cancers has not been well characterized due to the lack of adequate data and efficient computational tools. Here, we examine whole-genome sequencing data of 3,244 trios from 12 birth defect and childhood cancer cohorts in the Gabriella Miller Kids First Pediatric Research Program. Using an improved version of our tool xTea (x-Transposable element analyzer) that incorporates a deep-learning module, we identified 162 DNRTs, as well as 2 pseudogene insertions. Several variants are likely to be causal, such as a insertion that led to the ablation of a whole exon in the gene in a proband with brain tumor. We observe a high SVA insertion burden in both high-intolerance loss-of-function genes and exons as well as more frequent insertions of paternal origin. We also identify potential mosaic DNRTs from embryonic stages. Our study reveals the important roles of DNRTs in causing birth defects and predisposition to childhood cancers.
PubMed: 38699361
DOI: 10.1101/2024.04.15.24305733 -
Frontiers in Cellular and Infection... 2024Diagnosing poses challenges, and it's unclear if its rare isolation is due to infrequent occurrence or its fastidious nutritional requirements.
INTRODUCTION
Diagnosing poses challenges, and it's unclear if its rare isolation is due to infrequent occurrence or its fastidious nutritional requirements.
METHODS
This study analyzes the complete genome sequence of , obtained directly from the pus of a sternum infection in a lung transplant patient using metagenomic sequencing.
RESULTS
Genome analysis revealed limited therapeutic options for the infection, primarily susceptibility to tetracyclines. Three classes of mobile genetic elements were identified: two new insertion sequences, a new prophage (phiUMCG-1), and a species-specific variant of a mycoplasma integrative and conjugative element (MICE). Additionally, a Type I Restriction-Modification system was identified, featuring 5'-terminally truncated pseudogenes with overlapping repeats, indicating the potential for forming alternative variants through recombination.
CONCLUSION
This study represents the first-ever acquisition of a complete circularized bacterial genome directly from a patient sample obtained from invasive infection of a primary sterile site using culture-independent, PCR-free clinical metagenomics.
Topics: Humans; Metagenomics; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Mycoplasma; Mycoplasma Infections; Whole Genome Sequencing; Lung Transplantation; Prophages; Interspersed Repetitive Sequences; Anti-Bacterial Agents
PubMed: 38694516
DOI: 10.3389/fcimb.2024.1368923 -
BMC Biology May 2024Sex-limited chromosomes Y and W share some characteristics, including the degeneration of protein-coding genes, enrichment of repetitive elements, and heterochromatin....
BACKGROUND
Sex-limited chromosomes Y and W share some characteristics, including the degeneration of protein-coding genes, enrichment of repetitive elements, and heterochromatin. However, although many studies have suggested that Y chromosomes retain genes related to male function, far less is known about W chromosomes and whether they retain genes related to female-specific function.
RESULTS
Here, we built a chromosome-level genome assembly of the Asian corn borer, Ostrinia furnacalis Guenée (Lepidoptera: Crambidae, Pyraloidea), an economically important pest in corn, from a female, including both the Z and W chromosome. Despite deep conservation of the Z chromosome across Lepidoptera, our chromosome-level W assembly reveals little conservation with available W chromosome sequence in related species or with the Z chromosome, consistent with a non-canonical origin of the W chromosome. The W chromosome has accumulated significant repetitive elements and experienced rapid gene gain from the remainder of the genome, with most genes exhibiting pseudogenization after duplication to the W. The genes that retain significant expression are largely enriched for functions in DNA recombination, the nucleosome, chromatin, and DNA binding, likely related to meiotic and mitotic processes within the female gonad.
CONCLUSIONS
Overall, our chromosome-level genome assembly supports the non-canonical origin of the W chromosome in O. furnacalis, which experienced rapid gene gain and loss, with the retention of genes related to female-specific function.
Topics: Animals; Moths; Female; Sex Chromosomes; Chromosomes, Insect; Male; Evolution, Molecular; Genome, Insect
PubMed: 38693535
DOI: 10.1186/s12915-024-01902-4